RESUMO
Dengue fever is a clinical manifestation of dengue virus (DENV) infection well defined by the intense host immune response with the development of high fever, anorexia, headache and muscle pain. Several immune mediators are involved in the pathophysiology of DENV infection, in which polymorphisms in immune molecule genes contribute with the susceptibility and severity of the infection. Several meta-analyses are available with significant findings in the association between genetic variants in immune-mediator genes and dengue, though the results may be false positive. Hence, to solve this issue, we have performed a systematic revaluation with Bayesian approaches to verify the false positive rate in these results. A systematic search was performed for meta-analytic studies on the aforementioned issue. The calculations of false positive report probability (FPRP) and the Bayesian false-discovery probability (BFDP) at the prior probability of 10-3 and 10-6 have been performed. To verify the methodological quality of the studies included, the evaluation by the Venice criteria was applied. In addition, gene-gene and protein-protein networks were designed. As results, seven meta-analyses on genetic variants in several immune-inflammatory mediator genes and DENV infection comprise the results. Only the polymorphisms in the TNF, MICB, PLCE1, VDR, CD32 and HLA-A genes were considered as noteworthy. There was a heterogeneity profile for the results on Venice criteria indicating variability in the methodological quality. The gene-gene and protein-protein networks showed these immune mediators as relevant players in the disease. We suggest these polymorphisms as potential biomarkers for the pathogenesis and immune response against DENV.
Assuntos
Dengue , Viroses , Teorema de Bayes , Dengue/genética , Predisposição Genética para Doença/genética , Humanos , Metanálise como Assunto , Polimorfismo Genético/genéticaRESUMO
Periodontitis is a high prevalent disease into the clinical dentistry. Genetic variations in interleukins (IL) genes were associated with chronic periodontitis (CP) and were focus of several meta-analyses. This study aimed to assess the noteworthiness in the meta-analyses by means of a Bayesian approach to determinate possible false report associations. A systematic search was performed for meta-analyses with associations between gene polymorphisms in interleukins and CP. The calculations for the False-Positive Rate Probability (FPRP) and the Bayesian False Discovery Probability (BFDP) were performed to assess the noteworthiness with a statistical power of 1.2 and 1.5 of Odds Ratio at a prior probability of 10-3 and 10-6. As results, eight meta-analyses approaching the IL1A/rs1800587, IL1B/rs1143634, IL1RN/rs2234663, IL4/rs2243250, IL6/rs1800795/rs1800796, IL17A/rs2275913 and IL18/rs1946518/rs187238 polymorphisms have been identified. Twenty-two from 270 calculations (8.15%) were noteworthy. Herein, we have identified the IL1A and IL1B polymorphisms as noteworthy biomarkers for CP susceptibility.
Assuntos
Periodontite Crônica/genética , Predisposição Genética para Doença , Interleucina-1beta/genética , Polimorfismo de Nucleotídeo Único , Teorema de Bayes , Biomarcadores/metabolismo , Reações Falso-Positivas , Humanos , Mediadores da Inflamação , Metanálise como Assunto , Razão de Chances , ProbabilidadeRESUMO
BACKGROUND AND OBJECTIVE: Periodontitis may crosstalk with renal diseases, yet that remains unclear. We investigated whether the renal alterations caused by induced periodontitis are reversible after removal of the ligatures in experimental ligature-induced periodontitis. MATERIAL AND METHODS: Twenty-four female rats were divided into three groups: control (without periodontitis), periodontitis (20 days of ligature-induced periodontitis), and P20-20 (20 days of ligature-induced periodontitis and 20 days after ligature removal). The following periodontal parameters were assessed: gingival bleeding index, probing pocket depth, myeloperoxidase activity, and alveolar bone height. For renal tissues, histopathology, malonaldehyde (MDA) levels, glutathione (GSH) content, and renal weight were evaluated. In the blood, creatinine, uric acid, albumin, total cholesterol, total protein, and glucose levels were assessed. Total protein and creatinine levels in urine were also investigated. RESULTS: Rat renal tissues did not demonstrate reversal of periodontitis-related changes in the P20-20 group in terms of MDA, GSH, and histopathological evaluations when compared to the periodontitis group. Accordingly, only total cholesterol levels were reversible in the P20-20. CONCLUSION: Renal alterations caused by ligature-induced periodontitis persisted even after removal of ligatures in rats.
Assuntos
Perda do Osso Alveolar , Periodontite , Perda do Osso Alveolar/etiologia , Animais , Feminino , Ligadura , Malondialdeído , Periodontite/complicações , Ratos , Ratos WistarRESUMO
BACKGROUND AND OBJECTIVE: This study aimed to assess the effectiveness of the treatment with alpha-terpineol (αTPN) complexed with beta-cyclodextrin (ßCD) on oral, blood, and hepatic parameters in ligature-induced periodontitis. MATERIAL AND METHODS: Forty female rats were distributed among the following groups: control (vehicle solution), periodontitis (ligature + vehicle solution), 5 mg/kg of αTPN-ßCD (ligature), and 25 mg/kg of αTPN-ßCD (ligature). Compounds were administered daily via intraperitoneal injection over a 20-day period. Periodontitis was induced with the bilateral insertion of ligatures around the first lower molars of each rat. Oral parameters, as well as blood biomarkers, were measured: histopathological assessment of the hepatic tissue was carried out using light and transmission electron microscopy. RESULTS: The treatment with αTPN-ßCD significantly improved several oral parameters and blood biomarkers in comparison with rats with periodontitis. In addition, the treatment with αTPN-ßCD significantly ameliorated the steatosis score and reduced the number of lipid droplets and the amount of foamy cytoplasm in the hepatocytes of rats with periodontitis. CONCLUSION: The results obtained suggest that the treatment with αTPN-ßCD improves several oral and blood parameters in rats with experimental periodontitis. In addition, hepatic alterations caused by periodontitis were ameliorated in the rats treated with αTPN-ßCD.
Assuntos
Perda do Osso Alveolar , Monoterpenos Cicloexânicos , Periodontite , beta-Ciclodextrinas , Perda do Osso Alveolar/tratamento farmacológico , Perda do Osso Alveolar/prevenção & controle , Animais , Monoterpenos Cicloexânicos/farmacologia , Feminino , Ligadura , Periodontite/tratamento farmacológico , RatosRESUMO
BACKGROUND: Chronic periodontitis (CP) is an immune-inflammatory disease that promotes tissue damage around the teeth. Among the several inflammatory mediators that orchestrate the periodontitis, there is the interleukin (IL)-2. Genetic variations in IL2 gene may be associated with the risk and severity of the disease. Contrary results are available in the literature with inconclusive findings and none meta-analysis to gather these data. METHODS: A literature search was performed for studies published before June 11, 2019 in diverse scientific and educational databases. The data was extracted by two investigators and the statistical evaluation was performed by Review Manager statistical program with heterogeneity (I2) and Odds Ratio (OR) with 95% of Confidence Intervals (CI) calculations and a sensitive analysis to assess the accuracy of the obtained results. The publication bias was evaluated by Begg' and Egger's test with Comprehensive meta-analysis software. The value of P < 0.05 was considered as significant. RESULTS: Five studies were identified in diverse ethnical groups with 1425 participants. The - 330 T/G polymorphism in IL2 gene was not significantly associated with CP in allelic evaluation (P > 0.05) as well as in the genotypic comparisons (P = 0.15). The Begg's test and the linear regression Egger's test did not show any evidence of publication bias risk (P > 0.05) which was corroborated by the absence of obvious asymmetry in Funnel plot graphic. CONCLUSIONS: This meta-analysis showed a non-significant association between - 330 T/G polymorphism in IL2 gene and CP in any allelic evaluation.
Assuntos
Periodontite Crônica/genética , Predisposição Genética para Doença/genética , Interleucina-2/genética , Alelos , Predisposição Genética para Doença/etnologia , Humanos , Polimorfismo Genético , Polimorfismo de Nucleotídeo Único , Fatores de RiscoRESUMO
Polymorphisms in inflammatory genes such as interleukins 17A and 17F are associated with the risk of development of periodontitis, although the results remain contradictory. Hence, the aim of this study was perform a meta-analysis focusing on two polymorphisms (rs2275913 and rs763780) in interleukins 17A and 17F genes, respectively, in both chronic (CP) and aggressive periodontitis (AgP). A review in literature was performed in several databases for studies published before 25, September 2016. The meta-analysis was obtained through the review manager statistical software (version 5.2) with odds ratio (OR) calculation and funnel plot (P < 0.05) for heterogeneity, as well as the comprehensive meta-analysis software (version 3.3.070) for the assessment of publication bias. Seven articles with 1540 participants composed the results in which the mutant allele in the rs2275913 polymorphism did not present significant association with the risk of CP or AgP (OR 1.56, 95% CI 0.77, 3.15, P = 0.21; OR 1.12, 95% CI 0.05, 23.44, P = 0.94, respectively) nor was the mutant allele in rs763780 associated with the risk of CP (OR 1.19, 95% CI 0.80, 1.76, P = 0.39) or AgP (OR 1.07, 95% CI 0.63, 1.84, P = 0.79). No bias of publication was observed by Egger's and Begg's tests in any allelic evaluation. This meta-analysis showed a non-significant association between the polymorphisms rs2275913 and rs763780 in interleukins 17A and 17F genes and chronic and aggressive periodontitis in the allelic evaluation.
Assuntos
Interleucina-17/genética , Periodontite/genética , Adulto , Alelos , Estudos de Casos e Controles , Frequência do Gene/genética , Predisposição Genética para Doença/genética , Humanos , Interleucina-17/metabolismo , Razão de Chances , Polimorfismo de Nucleotídeo Único/genética , Fatores de RiscoRESUMO
The Euterpe genus (mainly Euterpe oleracea Martius, Euterpe precatoria Martius, and Euterpe edulis Martius) has recently gained commercial and scientific notoriety due to the high nutritional value of its fruits, which are rich in polyphenols (phenolic acids and anthocyanins) and have potent antioxidant activity. These characteristics have contributed to the increased number of neuropharmacological evaluations of the three species over the last 10 years, especially açaí of the species Euterpe oleracea Martius. The fruits of the three species exert neuroprotective effects through the modulation of inflammatory and oxidative pathways and other mechanisms, including the inhibition of the mTOR pathway and protection of the blood-brain barrier, all of them intimately involved in several neuropathologies. Thus, a better understanding of the neuropharmacological properties of these three species may open new paths for the development of therapeutic tools aimed at preventing and treating a variety of neurological conditions.
Assuntos
Euterpe , Antocianinas , Neuroproteção , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Frutas , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêuticoRESUMO
The association of polymorphisms in genes responsible for immunological mediators with dengue allows the identification of certain genetic alterations that increase or decrease the development risk of the disease. A few number of studies that correlate the interleukin 6-174 G > C (IL6-174 G > C) polymorphism (rs1800795) with dengue. However, there is an inconsistency on the polymorphism influence on the disease which motivated this meta-analysis. So, this study aimed to evaluate the rs1800795 polymorphism with protection or susceptibility for development of dengue. A search of the literature was performed for studies published before 05 September 2020 in various databases. Calculations of Odds Ratio (OR) with 95% of Confidence Intervals (CI) and heterogeneity (I2) were assessed and publication bias was done by Begg' and Egger's test. The value of P < 0.05 was considered as significant. As results, five case-control studies were identified and included in the results. The analysis showed that the heterozygous genotype has a protective role against dengue without warning signs (DWOS) (OR = 0.57, p = 0.001), as well as the polymorphic C allele (OR = 0.77, p = 0.04). When unifying the data from the included studies, the GG genotype was more prevalent among individuals with dengue with warning signs (DWWS) when compared to the control group (p = 0.0221). GC genotype was more prevalent in the control group than in the DWWS group (p = 0.0119). Therefore, in our study we observed that the GC genotype and the C allele have a protective role against DWOS. Since this polymorphism is associated with low IL-6 expression, thus it is expected that there will be a decreased pro-inflammatory response. However, more studies regarding this thematic are necessary to have a consensus about this polymorphism and dengue.
Assuntos
Dengue/genética , Predisposição Genética para Doença , Interleucina-6/genética , Polimorfismo de Nucleotídeo Único , Dengue/epidemiologia , Suscetibilidade a Doenças/epidemiologia , Estudos de Associação Genética , Predisposição Genética para Doença/epidemiologia , Humanos , Interleucina-6/metabolismo , Fatores de RiscoRESUMO
Objective Quantitatively evaluate blood parameters of the erythrocyte lineage in patients with chronic periodontitis and healthy controls by means of a meta-analysis. Material and methods A review of literature was performed in the scientific databases for studies published before September 2016. The abstracts were evaluated and the extraction of data performed by two examiners. The parameters assessed were: hemoglobin levels, number of circulating red blood cells, hematocrit, mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration in patients with chronic periodontitis and healthy controls. The calculations were obtained through the statistical software Review Manager version 5.3, with calculation of Mean Difference, heterogeneity (I²) and funnel plot with P < 0.05. Results Nine case/control studies composed the results with 342 patients with chronic periodontitis and 359 healthy controls. There was a significant decrease in hemoglobin levels (MD = -1.60, 95% CI: -2.72, -0.48, P = 0.005) and number of circulating red blood cells (MD = -0.51, 95% CI: -0.78, -0.24, P = 0.0002), hematocrit (MD = -4.41, IC 95%: -7.13, -1.68, P = 0.002), mean corpuscular hemoglobin (MD = -0.80; IC 95%: -1.38, -0,22, P = 0.007) and mean corpuscular hemoglobin concentration (MD = -0.93, IC 95%: -1.63, -0.23, P = 0.009) in patients with chronic periodontitis when compared to healthy controls. No publication bias was found through the funnel plot asymmetry. Conclusion There is an associated of the reduction of hematological parameters (such as levels of hemoglobin and circulating red blood cells, hematocrit, mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration) to patients with chronic periodontitis.
Assuntos
Periodontite Crônica/sangue , Índices de Eritrócitos , Estudos de Casos e Controles , HumanosRESUMO
Sulfated polysaccharides (PLS) extracted from the marine algae of the genus Gracilaria showed biological activity in different inflammatory models, except for periodontitis. Thus, this study aimed to evaluate the effectiveness of the treatment with PLS from Gracilaria caudata in ligature-induced periodontitis. 40 animals distributed into 5 groups were used (the control group (unligated), the ligated untreated group, and the ligated groups treated with 2.5, 5.0 and 10.0â¯mg/kg of PLS with intraperitoneal injection, respectively). After 20â¯days of treatment, the animals were killed and the following parameters were evaluated: Gingival Bleeding Index (GBI), Probing Pocket Depth (PPD), Myeloperoxidase (MPO) activity, Alveolar Bone Loss (ABL) for periodontal tissues; histopathological examination of gingival and liver tissues (Steatosis score); glutathione and malondialdehyde concentrations in the liver, serum levels of alanine aminotransferase and aspartate aminotransferase. The data revealed that treatment with 2.5â¯mg/kg of PLS showed the best anti-inflammatory effects with reduction of GBI, PPD and MPO activity, as well as oxidative stress and steatosis in liver. Our results indicated that the adjunct treatment with PLS from Gracilaria caudata could prevent the periodontal and hepatic tissue alteration caused by periodontitis.
Assuntos
Gracilaria/química , Periodontite/patologia , Polissacarídeos/química , Polissacarídeos/farmacologia , Sulfatos/química , Animais , Biomarcadores/metabolismo , Citoproteção/efeitos dos fármacos , Feminino , Ligadura/efeitos adversos , Fígado/efeitos dos fármacos , Fígado/patologia , Malondialdeído/metabolismo , Tamanho do Órgão/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Periodontite/etiologia , Periodontite/metabolismo , Ratos , Ratos WistarRESUMO
Several factors are involved in the periodontitis with host response through cytokines and as well as with influence of polymorphisms in cytokine genes, however the results remained contradictory. This study aimed at evaluating the rs1143634 polymorphism in interleukin-1B gene, a cytokine gene, and the risk of chronic periodontitis with conducting a meta-analysis focusing in ethnicity. A review in literature was performed in several databases to studies published before June 2017. Data extraction was performed by two calibrated investigators and the calculations of the meta-analysis were obtained through Review Manager version 5.2 statistical software with Odds Ratio (OR) calculation and Funnel plot (Pâ¯<â¯0.05) to heterogeneity and the Comprehensive Meta-analysis version 3.3.070 to assessment publication bias by Egger's and Begg's tests. In overall, 54 case/control studies composed the meta-analysis. T allele was significantly associated with patients case (ORâ¯=â¯1.35, 95% CI: 1.24, 1.48, Pâ¯<â¯0.00001) in the overall analysis. The stratified evaluation showed the rs1143634 polymorphism had significant association with disease in Caucasian, Asian and mixed population was excepted in African ethnicity (Pâ¯>â¯0.05). No publication bias was found in allelic evaluation. This meta-analysis in 9376 participants with 54 case/control studies revealed the rs1143634 polymorphism was associated with elevated risk of chronic periodontitis in overall analysis as well as Caucasian and Asian ethnicities and Mixed population.
Assuntos
Periodontite Crônica/genética , Interleucina-1beta/genética , Polimorfismo Genético , Alelos , Estudos de Casos e Controles , HumanosRESUMO
Purpose. This work aimed to synthesize the results of recent meta-analysis focusing on polymorphism in inflammatory mediators and its relation with the risk of periodontitis development. Materials and Methods. A systematic search was conducted using databases for publications prior to October 2016. Three examiners extracted data from articles with a clear association between polymorphisms in the inflammatory mediator gene and the development of periodontitis through meta-analysis using the fixed or randomized statistical models to calculate the Odds Ratio with values of P < 0.05 considered significant. Results. A total of 13 meta-analysis articles with 25 polymorphisms in seven interleukins (IL-1A, IL-1B, IL-4, IL-6, IL-8, IL-10, and IL-18), three cellular receptors (Fcγ receptors: FCGR2A, FCGR3A, and FCGR3B), and five inflammatory mediators (COX-2, MMP-2, MMP-3, MMP-8, and MMP-9), with a total of 71,531 participants, approaching different classifications of the disease. Conclusion. The study demonstrated that polymorphisms in the IL-1A, IL-1B, IL-6, IL-10, MMP-3 (chronic form), and MMP-9 (chronic form) polymorphisms were significantly associated with the risk of developing periodontitis, whereas other polymorphisms in the IL-4, IL-8, IL-18, Fcγ, COX-2, MMP-2, MMP-3 (aggressive), MMP-8, and MMP-9 (aggressive) polymorphisms had no significant association with risk of developing periodontitis.