Publications by authors named "Raul Emídio Lima"

11 Publications

  • Page 1 of 1

TXNRD2 (rs35934224) CT genotype as possible protective marker for primary open-angle glaucoma in a Brazilian population.

Arq Bras Oftalmol 2021 Aug 18. Epub 2021 Aug 18.

Instituto Aggeu Magalhães, Campus da Universidade Federal de Pernambuco, Recife, PE, Brazil.

Purpose: To investigate the association of the single-nucleotide polymorphism rs35934224 in the TXNRD2 gene with primary open-angle glaucoma in a Brazilian population.

Methods: This was a cross-sectional study conducted to verify the association between the rs35934224 TXNRD2 (thioredoxin reductase 2) and primary open-angle glaucoma in a population from the Northeast region of Brazil. A total of 184 individuals were enrolled, including 94 with primary open-angle glaucoma (45 men and 49 women) and 94 controls (40 men and 54 women) from the Recife Eye Institute.

Results: The mean age was 68.85 years for the patients with glaucoma and 68.55 years for the controls. Genomic DNA was isolated using commercially available kits, and single-nucleotide polymorphism was detected with real-time polymerase chain reaction using TaqMan probes. The studied population was in Hardy-Weinberg equilibrium. The CT genotype was associated with protection against primary open-angle glaucoma (p=0.022).

Conclusion: Our data suggest an association between TXNRD2 gene polymorphism (rs35934224) with primary open-angle glaucoma in an admixed Brazilian po pulation. This is the first study to investigate this single-nucleo tide polymorphism in Latin American individuals with primary open-angle glaucoma.
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http://dx.doi.org/10.5935/0004-2749.20220019DOI Listing
August 2021

Potential role of microRNAs as biomarkers in human glioblastoma: a mini systematic review from 2015 to 2020.

Mol Biol Rep 2021 May 25;48(5):4647-4658. Epub 2021 May 25.

Laboratório de Biologia Molecular de Doenças Infecciosas, Departamento de Parasitologia, Instituto Aggeu Magalhães (IAM), Fundação Oswaldo Cruz (FIOCRUZ), 50670-420, Recife, Pernambuco, Brasil.

Glioblastoma (GBM) is the most common, aggressive and malignant type of glioma, with poor prognosis, despite advances in medical knowledge and technology. It's known that some microRNAs (miRNAs) can be dysregulated and associated with tumors. We aim to investigate miRNAs that may have a role as potential biomarkers in human glioblastoma. A search was performed using PubMed, LILACS and SCIELO databases to find papers from 2015 to 2020, related to human in vitro and ex vivo data. From 99 articles, 10 were eligible and 13 dysregulated miRNAs were found with description of regulation, target(s), pathway(s) and mechanism(s). The miRNAs of interest were found and seem to be involved in development and progression of glioblastoma and used as target therapies. Understanding the mechanisms in which those miRNAs are involved and their role in epigenetic pathways that lead to cancer, as well as their potential in clinical application, may improve GBM clinical outcome (CRD42020182706, 07/10/2020, retrospectively registered).
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http://dx.doi.org/10.1007/s11033-021-06423-9DOI Listing
May 2021

Influence of LGALS3 and PNPLA3 genes in non-alcoholic steatohepatitis (NASH) in patients undergone bariatric surgery.

Obes Res Clin Pract 2020 Jul - Aug;14(4):326-332. Epub 2020 Jul 18.

School of Medical Sciences, University of Pernambuco, Brazil; Institute of Liver and Transplant of Pernambuco, Brazil.

Aim: This study evaluated the genesPNPLA3 and LGALS3 in patients who have undergone bariatric surgery.

Methods: Individuals with NAFLD and NASH were evaluated, the DNA was extracted from total blood for genotyping of rs4644, rs4652 from LGALS3 and rs738409 from PNPLA3 genes, the total RNA was obtained from liver biopsy. For the detection of the molecular targets, real-time PCR through Taqman probes was used.

Results: From a total of 46 collected patients, of those 21 (456%) were included as NASH and 25 (544%) as steatosis group. This groups showed significant difference to aspartate aminotransferase (AST), alanine aminotransferase (ALT) and Glutamyl transpeptidase (GGT) (p = 0.0108, p = 0.0090 and p = 0.0044). Regarding to gene expression in studied groups, hepatic steatosis vs NASH, we observed a higher expression of the LGALS3 gene in NASH (p = 0.0273). In addition, patients with C allele in homozygous for rs4644 and rs4652 of LGALS3 gene had higher expression, in NASH group (p = 0.0500 and p = 0.0242, respectively), furthermore for rs4644 both alleles in homozygous showed higher expression (AA/CC vs AC) (p = 0.0500), when analyzed PNPLA3 rs738409, NASH patients with G allele in homozygous had higher expression (p = 0.0494).

Conclusions: Therefore, an increased expression of the LGALS3 gene in patients with NASH may be important in the etiopathogenesis of the disease, as well as the presence of rs4652 and rs4644 SNPs in the regulation of transcriptional levels of the gene in patients with NAFLD and NASH.
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http://dx.doi.org/10.1016/j.orcp.2020.07.004DOI Listing
August 2021

Polymorphisms of and genes related to time in therapeutic range in patients with atrial fibrillation using warfarin.

Appl Clin Genet 2019 2;12:151-159. Epub 2019 Aug 2.

Pronto Socorro Cardiológico Professor Luiz Tavares - PROCAPE/UPE , Recife, Brazil.

Introduction: Warfarin continues to be the most widely used anticoagulant in clinical practice around the world for the prevention of thromboembolic events in patients with atrial fibrillation (AF). The evaluation of the quality of anticoagulation control, estimated by time in therapeutic range (TTR), is accepted as a good method to evaluate the quality of anticoagulation. The variability of TTR can be explained by the presence of variants of the and genes.

Methods: This study examined the association between polymorphisms of the  and  genes and control of oral anticoagulation, through TTR, in patients with AF. A cross-sectional study was conducted within a cohort follow-up. The study comprised of 317 patients with AF, using warfarin, who were followed up for one year. The genotyping of genes (rs1057910), (rs1799853) and (rs923231) was performed by PCR in real time, using TaqMan probes.

Results: Patients who had variant genotypes for the gene (rs1057910) presented higher TTR (TTR 81-100%) when compared to when compared to the <45% and 46-60% TTR groups (=0.005 and =0.002, respectively). Regarding (rs923231), patients who had the variant genotype for the (rs923231) gene also presented a higher TTR (TTR 81-100%), when when compared to the <45% and 46-60% TTR groups (=0.005 and =0.004, respectively). In a multivariate model, (rs923231) remained associated for comparisons with the TTR groups (<45% vs 81-100% groups, =0.01; and 46-60% vs 81-100% groups, =0.01).

Conclusion: The genotypes of the (AA) and -1639 (GG) genes were associated with the worst quality of anticoagulation control (TTR) in patients with AF using warfarin in the northeast of Brazil.
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http://dx.doi.org/10.2147/TACG.S197316DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6684853PMC
August 2019

Expression of microRNAs (133b and 138) and Correlation with Echocardiographic Parameters in Patients with Alcoholic Cardiomyopathy.

Microrna 2020 ;9(2):112-120

Faculdade de Ciencias Medicas/ Universidade de Pernambuco - FCM/UPE, Recife, Pernambuco, Brazil.

Introduction: Alcoholic Cardiomyopathy (ACM) is a disease with a difficult diagnosis. The real mechanisms related to its pathophysiology are not fully understood.

Objective: The aims of this study were to investigate whether miR-133b and miR-138 could be associated with ACM.

Methods: Forty-four patients were included comprising 24 with ACM and 20 with cardiomyopathies of different etiologies (control group). Real-time PCR was performed to verify the relative expression among the studied groups. In the statistical analysis, the quantitative variables t-student Mann- Whitney and correlation of Pearson tests were carried out, while the qualitative variable comprised the chi-square test, with p<0.05 being considered statistically significant.

Results: There was no association between clinical and sociodemographic characteristics of the groups. The patients with ACM presented downregulation of miR-133b in comparison with control patients (p=0.004). On the other hand, for the miR-138, there was no association when the ACM group was compared with the control group. The presence of miR-133b among cases and controls was not correlated with any of the echocardiographic parameters. However, the increase in the expression of miR-138 was correlated with an increase in the ejection fraction (r=0.28, p=0.01) and the diameter of the left atrium (r=0.23, p=0.04) in patients with ACM.

Conclusion: The downregulation of miR-133b might be a marker for ACM and, in addition, miR- 138 could be used to correlate the increase in ejection fraction with and normalization of the diameter of the left atrium diameter in patients with this disease.
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http://dx.doi.org/10.2174/2211536608666190716151900DOI Listing
May 2021

AA Variant Genotype (G2431A, rs3739319) Is Associated with Severe Dengue Risk Development in a DEN-3 Brazilian Cohort.

Viral Immunol 2019 09 13;32(7):296-301. Epub 2019 Jun 13.

Department of Virology, Aggeu Magalhães Institute, Oswaldo Cruz Foundation (FIOCRUZ). Recife/PE, Brazil.

Dengue is considered one of the most challenging public health threats in the world. Infection may be clinically asymptomatic but can result in severe forms. The indoleamine 2,3 dioxygenase () gene encodes one of first enzymes () of the kynurenine pathway. This study aimed to verify the association between G2431A gene single nucleotide polymorphism (SNP) (rs3739319) and dengue fever development. We included 299 dengue-infected individuals in the study and 96 dengue-free controls. We collected clinical and diagnostic test data and divided the patients with dengue infection into three groups, based on World Health Organization (WHO) criteria: 131 Dengue without warning signs (DWOS), 143 Dengue with warning signs (DWS), and 25 severe dengue (SD). We genotyped 193 of the dengue cases using quantitative polymerase chain reaction to the SNP rs3739319. The other 106 dengue cases and 96 dengue-free controls had previously been genotyped using the Illumina Genotyping Kit. Genotyping of the infected patients revealed frequencies of 106 GG (35.4%), 126 GA (42.1%), and 67 AA (22.4%), whereas the nondengue exposed control group showed similar frequencies, 29 GG (30.2%), 52 GA (54.2%), and 15 AA (15.6%). Under risk analysis we found that AA genotype patients had a higher risk of developing SD in a codominant model (AA × GG; odds ratio [OR] = 11.5-fold in comparison to non-SD group -DWOS and -DWS patients; confidence interval [CI] = 0.02-0.32; Yates correction = 1.9e-05) and in a recessive model (AA × AG+GG; OR = 9.41; CI = 3.62-26.7; Yates correction = 4.8e-08). An allelic model reinforced the association between A allele and SD phenotype development that was found in the SD versus DWOS+DWS analysis (OR = 3.59; CI = 1.50-9.56; Yates correction = 0.0033). Our data show an association between the G2431A variant and the risk for SD. This SNP may be relevant for further investigation into disease mechanisms and host factors in future genetic and pathophysiological studies.
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http://dx.doi.org/10.1089/vim.2018.0149DOI Listing
September 2019

Two sides of a coin: GG genotype of C7 provides protection against fibrosis severity while showing a higher risk for hepatocellular carcinoma in patients with hepatitis C.

Hum Immunol 2018 Sep 30;79(9):702-707. Epub 2018 Jun 30.

Institute of Biological Sciences/ICB-UPE, University of Pernambuco, Brazil.

The complement system (CS) is a key element of immunity against pathogens but also seems to influence other events, such as tumorigenesis and tissue repair. Complement component 7 (C7) is a key component of the lytic pathway of CS, leading to the formation of the membrane attack complex (MAC). This study aimed to investigate the existence of the association of a polymorphism in the C7 gene, rs1063499, with hepatic fibrosis and the occurrence of hepatocellular carcinoma (HCC) in patients with hepatitis C. We analyzed 456 samples from patients with chronic hepatitis C. Real-time PCR was used for allelic discrimination. Patients were classified by their METAVIR score as F1 (n = 100), F2 (n = 83), F3 (n = 101) or F4 (n = 66); 106 patients were diagnosed with HCC. Patients carrying the G/G genotype of C7 had a lower chance of developing severe fibrosis in the recessive model (p = 0.042; OR: 0.65 95% CI 0.41-1.02). However, the G/G genotype frequency was higher in patients with HCC (P = 0.01; OR: 2.07 95% CI 1.20-3.53) and in those with larger tumors (p = 0.04). The G/G C7 genotype seems to be a protective factor against advanced fibrosis; however, it was associated with a higher risk of HCC and the occurrence of larger hepatic nodules, suggesting the involvement of C7 in the physiopathogenesis of HCC and fibrosis in patients with hepatitis C virus (HCV).
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http://dx.doi.org/10.1016/j.humimm.2018.06.009DOI Listing
September 2018

Binding capacity of mannose-binding lectin (MBL) is associated with the severity of chronic Chagas cardiomyopathy.

Parasitol Int 2018 10 24;67(5):593-596. Epub 2018 May 24.

Aggeu Magalhães Institute, IAM-FIOCRUZ, PE, Brazil. Electronic address:

Chagas disease (CD) is a global problem. Currently, it affects approximately 15 million individuals in Latin America. It is well know that the human immune response is related to different clinical manifestations. Mannose binding lectin (MBL) plays an important role in innate immunity, and it mediates the phagocytosis and complement-mediated destruction of pathogens. The binding capacity is enhanced by the oligomerization of MBL. In this study, we evaluated the serum concentration and the binding capacity of MBL in patients with chronic chagasic cardiomyopathy. A total of 77 patients with chronic CD were included with indeterminate (n = 19), mild cardiac (n = 29) and severe cardiac (n = 29) forms. The serum concentration and the binding capacity were measured using enzyme-linked immunosorbent assays (ELISA). There was no significant difference in the serum MBL levels between the groups of patients. However, we found a relationship between the binding capacity and the groups studied. Our results suggest that binding capacity of MBL could be an indicator of clinical manifestation in Chronic Chagas cardiomyopathy. Furthermore, combined with the Mannose Binding Index results in a useful clinical tool for management of Chronic Chagas Patients.
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http://dx.doi.org/10.1016/j.parint.2018.05.009DOI Listing
October 2018

Cognitive Dysfunction and Single Nucleotide Polymorphisms in Hepatitis C Virus-Infected Persons: A Systematic Review.

Viral Immunol 2017 12 10;30(10):703-707. Epub 2017 Oct 10.

6 Hospital Universitário Oswaldo Cruz; Medical Sciences College, Universidade de Pernambuco (UPE) , Recife, PE, Brazil .

The aim of this study was to realize a systematic review to identify data reported in the literature involving people infected by hepatitis C virus (HCV) with cognitive dysfunctions and single nucleotide polymorphisms (SNPs). The research was realized in six databases and the selection of studies was performed in two stages. Initially, we searched indexed articles from the following electronic databases: SciELO, MEDLINE, PubMed, HighWire, LILACS, and ScienceDirect. Then the articles were completely read and those that did not meet the eligibility criteria were excluded. Therefore, 5,669 articles were obtained and, of these, 25 were selected. Finally, one article involving people with HCV and cognitive impairment was included in the review. The frequency of the APOE-ɛ4 allele in people with HCV and mild liver disease was significantly lower in those with work memory impairment (p = 0.003) and attention (p = 0.008). This situation differs from other studies that showed an association between ɛ4 allele high frequency and cognitive decline. Thus, studies with larger samples involving people with HCV, cognitive alterations, and SNPs are necessary, in view of the lack of this theme in the literature and the divergences in the findings.
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http://dx.doi.org/10.1089/vim.2017.0084DOI Listing
December 2017

TNF-α and IL-10 polymorphisms increase the risk to hepatocellular carcinoma in HCV infected individuals.

J Med Virol 2016 09 21;88(9):1587-95. Epub 2016 Mar 21.

Setor de Virologia do Laboratório de Imunopatologia Keizo-Asami (LIKA), Universidade Federal de Pernambuco (UFPE), Brazil.

Hepatitis C virus (HCV) is the major cause of hepatocellular carcinoma (HCC). The risk to develop HCC increases with the severity of liver inflammation and hepatic fibrosis. It is believed that a balance between the releases of pro- and anti-inflammatory cytokines will determine the clinical course of HCV and the risk to develop HCC. The inteleukin-10 (IL-10) and the tumor necrosis factor alpha (TNF-α) play key roles in the Th1 and Th2 balance during the inflammatory response against HCV. The aim of the present study was to investigate the association between polymorphisms in TNF-α -308 G>A (rs1800629), IL-10 -1082 G>A (rs1800896) and -819/-592 (rs1800871/rs1800872) with HCC risk in individuals with HCV. The present study evaluated 388 chronic HCV patients. Polymorphisms were determined by real-time PCR. Diplotypes associated with low IL-10 production and the TNF-α GG genotype were significantly associated with HCC occurrence after multivariate logistic regression analysis (P = 0.027 and P = 0.029, respectively). Additionally, the IL-10 -819 (-592) TT (AA) genotype was significantly associated with multiple nodules and HCC severity according to BCLC staging (P = 0.044 and P = 0.025, respectively). Patients carrying low production haplotypes of IL-10 and the TNF-α GG genotype have higher risk to develop HCC. J. Med. Virol. 88:1587-1595, 2016. © 2016 Wiley Periodicals, Inc.
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http://dx.doi.org/10.1002/jmv.24501DOI Listing
September 2016
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