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

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).

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

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.

Spatiotemporal transmission of SARS-CoV-2 lineages during 2020-2021 in Pernambuco-Brazil.

SARS-CoV-2 virus emerged as a new threat to humans and spread around the world, leaving a large death toll. As of January 2023, Brazil is among the countries with the highest number of registered deaths. Nonpharmacological and pharmacological interventions have been heterogeneously implemented in the country, which, associated with large socioeconomic differences between the country regions, has led to distinct virus spread dynamics. Here, we investigate the spatiotemporal dispersion of SARS-CoV-2 lineages in the Pernambuco state (Northeast Brazil) throughout the distinct epidemiological scenarios that unfolded in the first 2 years of the pandemic. We generated a total of 1,389 new SARS-CoV-2 genomes from June 2020 to August 2021. This sampling captured the arrival, communitary transmission, and the circulation of the B1.1, B.1.1.28, and B.1.1.33 lineages; the emergence of the former variant of interest P.2; and the emergence and fast replacement of all previous variants by the more transmissible variant of concern P.1 (Gamma). Based on the incidence and lineage spread pattern, we observed an East-to-West to inner state pattern of transmission, which is in agreement with the transmission of more populous metropolitan areas to medium- and small-size country-side cities in the state. Such transmission patterns may be partially explained by the main routes of traffic across municipalities in the state. Our results highlight that the fine-grained intrastate analysis of lineages and incidence spread can provide actionable insights for planning future nonpharmacological intervention for air-borne transmissible human pathogens.IMPORTANCEDuring the COVID-19 pandemic, Brazil was one of the most affected countries, mainly due its continental-size, socioeconomic differences among regions, and heterogeneous implementation of intervention methods. In order to investigate SARS-CoV-2 dynamics in the state of Pernambuco, we conducted a spatiotemporal dispersion study, covering the period from June 2020 to August 2021, to comprehend the dynamics of viral transmission during the first 2 years of the pandemic. Throughout this study, we were able to track three significant epidemiological waves of transmission caused by B1.1, B.1.1.28, B.1.1.33, P.2, and P.1 lineages. These analyses provided valuable insights into the evolution of the epidemiological landscape, contributing to a deeper understanding of the dynamics of virus transmission during the early years of the pandemic in the state of Pernambuco.

Interferon-gamma gene diplotype (AA-rs2069716 / AG-rs2069727) may play an important role during secondary outcomes of severe dengue in Brazilian patients.

Dengue is a global and growing health threat, especially in Southeast Asia, West Pacific and South America. Infection by the dengue virus (DENV) results in dengue fever, which can evolve to severe forms. Cytokines, especially interferons, are involved in the immunopathogenesis of dengue fever, and so may influence the disease outcomes. The aim of this study was to investigate the association between severe forms of dengue and two single nucleotide polymorphisms (SNPs) in the interferon-gamma gene (IFNG): A256G (rs2069716) and A325G (rs2069727). We included 274 patients infected with DENV serotype 3: 119 cases of dengue without warning signs (DWoWS), and 155 with warning signs (DWWS) or severe dengue (SD). DNA was extracted, and genotyped with Illumina Genotyping Kit or real time PCR (TaqMan probes). We estimated the adjusted Odds Ratios (OR) by multivariate logistic regression models. When comparing with the ancestral AA/AA diplotype (A256G/A325G), we found a protective association of the AA/AG against DWWS/SD among patients with secondary dengue (OR 0.51; 95% IC 0.24-1.10, p = 0.085), adjusting for age and sex. The variant genotype at locus A325G of the IFNG, in combination with the ancestral genotype at locus A256G, can protect against severe clinical forms of secondary dengue in Brazilian DENV3-infected patients.

MicroRNA dysregulation in schistosomiasis-induced hepatic fibrosis: a systematic review.

BACKGROUND: MicroRNAs are involved in gene regulation in several common liver diseases and may play an essential role in activating hepatic stellate cells. The role of these post-transcriptional regulators in schistosomiasis needs to be further studied in populations from endemic areas for a better understanding of the disease, the development of new therapeutic approaches, and the use of biomarkers for the prognosis of schistosomiasis. AREAS COVERED: We performed a systematic review to describe the main human microRNAs identified in non-experimental studies associated with aggravation of the disease in people infected with Schistosoma mansoni (S. mansoni) and Schistosoma japonicum (S. japonicum). Structured searches were carried out in PubMed, Medline, Science Direct, Directory of Open Access Journals, Scielo, Medcarib, and Global Index Medicus databases without time and language restrictions. This is a systematic review following the guidelines of the PRISMA platform. EXPERT OPINION: The miR-146a-5p, miR-150-5p, let-7a-5p, let-7d-5p, miR-92a- 3p, and miR-532-5p are associated with liver fibrosis in schistosomiasis caused by S. japonicum, revealing that these miRNAs that have been shown to be associated with liver fibrosis are good targets for new studies that evaluate their potential as a biomarker or even treating liver fibrosis in schistosomiasis.

Assessment of clinical characteristics and viral load in individuals infected by Delta and Omicron variants of SARS-CoV-2.

In late 2021, a new variant of SARS-CoV-2 called Omicron emerged, replacing Delta worldwide. Although it has been associated with a lower risk of hospitalization and severe forms of COVID-19, there is little evidence of its relationship with specific symptoms and viral load. The aim of this study was to verify the relationship between Delta and Omicron variants of concern, viral load, and the occurrence of symptoms in individuals with COVID-19. Nasopharyngeal swab samples were collected and sequenced from patients with COVID-19 from the Northeast Region of Brazil between August 2021 and March 2022. The results showed a gradual replacement of the Delta variant by the Omicron variant during the study period. A total of 316 samples (157 Delta and 159 Omicron) were included. There was a higher prevalence of symptoms in Delta-infected individuals, such as coryza, olfactory and taste disturbances, headache, and myalgia. There was no association between viral load and the variants analyzed. The results reported here contribute to the understanding of the symptoms associated with the Delta and Omicron variants in individuals affected by COVID-19.

Real-life evaluation of a rapid antigen test (DPP SARS-CoV-2 Antigen) for COVID-19 diagnosis of primary healthcare patients, in the context of the Omicron-dominant wave in Brazil.

OBJECTIVES: We aimed to investigate the real-life performance of the rapid antigen test in the context of a primary healthcare setting, including symptomatic and asymptomatic individuals that sought diagnosis during an Omicron infection wave. METHODS: We prospectively accessed the performance of the DPP SARS-CoV-2 Antigen test in the context of an Omicron-dominant real-life setting. We evaluated 347 unselected individuals (all-comers) from a public testing centre in Brazil, performing the rapid antigen test diagnosis at point-of-care with fresh samples. The combinatory result from two distinct real-time quantitative PCR (RT-qPCR) methods was employed as a reference and 13 samples with discordant PCR results were excluded. RESULTS: The assessment of the rapid test in 67 PCR-positive and 265 negative samples revealed an overall sensitivity of 80.5% (CI 95% = 69.1%-89.2%), specificity of 99.2% (CI 95% = 97.3%-99.1%) and positive/negative predictive values higher than 95%. However, we observed that the sensitivity was dependent on the viral load (sensitivity in Ct < 31 = 93.7%, CI = 82.8%-98.7%; Ct > 31 = 47.4%, CI = 24.4%-71.1%). The positive samples evaluated in the study were Omicron (BA.1/BA.1.1) by whole-genome sequencing (n = 40) and multiplex RT-qPCR (n = 17). CONCLUSIONS: Altogether, the data obtained from a real-life prospective cohort supports that the rapid antigen test sensitivity for Omicron remains high and underscores the reliability of the test for COVID-19 diagnosis in settings with high disease prevalence and limited PCR testing capability.

Multiple introductions and country-wide spread of DENV-2 genotype II (Cosmopolitan) in Brazil.

Dengue virus serotype 2, genotype Cosmopolitan (DENV-2-GII), is one of the most widespread DENV strains globally. In the USA, DENV-2 epidemics have been dominated by DENV-2 genotype Asian-American (DENV-2-GIII), and the first cases of DENV-2-GII were only described in 2019, in Peru, and in 2021 in Brazil. To gain new information about the circulation of DENV-2-GII in Brazil, we sequenced 237 DENV-2 confirmed cases sampled between March 2021 and March 2023 and revealed that DENV-2-GII is already present in all geographic regions of Brazil. The phylogeographic analysis inferred that DENV-2-GII was introduced at least four times in Brazil, between May 2020 and August 2022, generating multiple clades that spread throughout the country with different success. Despite multiple introductions of DENV-2-GII, analysis of the country-wide laboratory surveillance data showed that the Brazilian dengue epidemic in 2022 was dominated by DENV-1 in most states. We hypothesize that massive circulation of DENV-2-GIII in previous years in Brazil might have created a population immune barrier against symptomatic homotypic reinfections by DENV-2-GII, leading to sustained cryptic circulation in asymptomatic cases and localized outbreaks of this new genotype. In summary, our study stresses the importance of arboviral genomic surveillance to close monitoring and better understanding the potential impact of DENV-2-GII in the coming years.

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

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.

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

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.

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

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.

AA IDO1 Variant Genotype (G2431A, rs3739319) Is Associated with Severe Dengue Risk Development in a DEN-3 Brazilian Cohort.

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 (IDO) gene encodes one of first enzymes (IDO) of the kynurenine pathway. This study aimed to verify the association between G2431A IDO1 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 IDO 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.

Polymorphisms of CYP2C9*2, CYP2C9*3 and VKORC1 genes related to time in therapeutic range in patients with atrial fibrillation using warfarin.

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 CYP2C9 and VKORC1 genes. METHODS: This study examined the association between polymorphisms of the CYP2C9 and VKORC1 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 CYP2C9 (rs1057910), (rs1799853) and VKORC1 (rs923231) was performed by PCR in real time, using TaqMan probes. RESULTS: Patients who had variant genotypes for the CYP2C9*3 gene (rs1057910) presented higher TTR (TTR 81-100%) when compared to when compared to the <45% and 46-60% TTR groups (p=0.005 and p=0.002, respectively). Regarding VKORC1 (rs923231), patients who had the variant genotype for the VKORC1 (rs923231) gene also presented a higher TTR (TTR 81-100%), when when compared to the <45% and 46-60% TTR groups (p=0.005 and p=0.004, respectively). In a multivariate model, VKORC1 (rs923231) remained associated for comparisons with the TTR groups (<45% vs 81-100% groups, p=0.01; and 46-60% vs 81-100% groups, p=0.01). CONCLUSION: The genotypes of the CYP2C9*3 (AA) and VKORC1 -1639 (GG) genes were associated with the worst quality of anticoagulation control (TTR) in patients with AF using warfarin in the northeast of Brazil.

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.

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).

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

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.

Interferon-gamma gene diplotype (AA-rs2069716 / AG-rs2069727) may play an important role during secondary outcomes of severe dengue in Brazilian patients

ABSTRACT Dengue is a global and growing health threat, especially in Southeast Asia, West Pacific and South America. Infection by the dengue virus (DENV) results in dengue fever, which can evolve to severe forms. Cytokines, especially interferons, are involved in the immunopathogenesis of dengue fever, and so may influence the disease outcomes. The aim of this study was to investigate the association between severe forms of dengue and two single nucleotide polymorphisms (SNPs) in the interferon-gamma gene (IFNG): A256G (rs2069716) and A325G (rs2069727). We included 274 patients infected with DENV serotype 3: 119 cases of dengue without warning signs (DWoWS), and 155 with warning signs (DWWS) or severe dengue (SD). DNA was extracted, and genotyped with Illumina Genotyping Kit or real time PCR (TaqMan probes). We estimated the adjusted Odds Ratios (OR) by multivariate logistic regression models. When comparing with the ancestral AA/AA diplotype (A256G/A325G), we found a protective association of the AA/AG against DWWS/SD among patients with secondary dengue (OR 0.51; 95% IC 0.24-1.10, p = 0.085), adjusting for age and sex. The variant genotype at locus A325G of the IFNG, in combination with the ancestral genotype at locus A256G, can protect against severe clinical forms of secondary dengue in Brazilian DENV3-infected patients.

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

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.