Association of salivary alpha-2-macroglobulin with glycemia and glycated hemoglobin in type 2 diabetes mellitus: a systematic review and meta-analysis study

Abstract BACKGROUND: Chronically elevated alpha-2-macroglobulin (A2MG) in the blood has been correlated with diabetes and the HbA1c profile; however, no systematic review has been conducted to evaluate the association of A2MG salivary levels and glycemia or HbA1c levels in diabetes mellitus type 2 (DM2) patients. OBJECTIVE: To evaluate whether A2MG salivary levels are related to the glycemia or HbA1c levels in DM2 patients. DESIGN AND SETTING: Systematic review developed at Universidade Federal de Uberlândia (UFU), Brazil. METHODS: Eight databases were used as research sources. The eligibility criteria included studies that reported data regarding mean salivary A2MG and the correlation between glycemia and/or HbA1c levels of DM2 subjects (uncontrolled and well-controlled) and non-diabetic subjects. The risk of bias of the studies selected was assessed using the Joanna Briggs Institute (JBI) critical appraisal tools for use in JBI systematic reviews. Pooled correlation coefficients were estimated using the Hunter-Schmidt method. Study estimates were weighted according to their sample size, and heterogeneity was calculated using the chi-square statistic. RESULTS: Four studies on DM2 patients were included in this systematic review after careful analysis of 1482 studies. Three studies compared A2MG with HbA1c and glycemia. Overall, the correlation between A2MG and HbA1c was strong (r = 0.838). In contrast, the correlation between A2MG and glycemia was low (r = 0.354). CONCLUSION: The strong association between HbA1C and salivary A2MG suggests that this salivary protein has the potential to be a surrogate for HbA1C, if corroboratory further evidence is obtained through large-scale studies.

Biomarcadores salivares do estresse oxidativo em crianças com cárie dentária: revisão sistemática e meta-análises / Salivary biomarkers of oxidative stress in children with dental caries: systematic review and meta-analysis

Objetivo. Avaliar a relação entre biomarcadores salivares de estresse oxidativo e cárie dentária em crianças. Métodos. Estudos realizados em crianças de até 12 anos comparando biomarcadores salivares de estresse oxidativo como malondialdeído (MDA), superóxido dismutase (SOD), ácido úrico, capacidade antioxidante total (TAC) e proteína total, considerando crianças com lesões de cárie dentária e sem cárie foram selecionados. Além disso, parâmetros salivares como fluxo salivar, pH, capacidade tampão e níveis de cálcio foram avaliados. Uma revisão sistemática da literatura foi realizada em 8 bases de dados. A diferença média padronizada (SMD) foi medida usando variância inversa como método estatístico e efeitos aleatórios como modelo de análise, correspondendo a um intervalo de confiança (IC) de 95%. Resultados. Os níveis de TAC foram maiores em crianças afetadas por cárie dentária em comparação com as sem cárie (grupo controle), independentemente da idade (SMD 2,66; IC 1,33; 3,98) ou sexo (SMD 0,98; IC 0,56; 1,39). Quando ajustados para proteína normalizada, os níveis de MDA foram menores no grupo de cárie dentária do que no grupo controle (SMD -16,5; IC - 29,02; -4,00), e os níveis de SOD foram maiores no grupo de cárie dentária (SMD 5,09; IC 0,01; 10,18). A concentração de proteína total na saliva de crianças com cárie dentária foi maior do que no grupo controle, independentemente da idade (SMD 0,98; IC 0,27; 1,69) ou sexo (SMD 0,77; IC 0,45; 1,10). Os parâmetros salivares avaliados apresentaram níveis mais baixos em crianças com cárie dentária (p< 0,05). Conclusões. Os níveis de biomarcadores de estresse oxidativo e parâmetros salivares estão alterados na saliva de crianças com cárie dentária(AU)

Objective. To assess the relationship between salivary biomarkers of oxidative stress and dental caries in children. Methods. Studies conducted in children up to 12 years old comparing salivary biomarkers of oxidative stress such as malondialdehyde (MDA), superoxide dismutase (SOD), uric acid, total antioxidant capacity (TAC), and total protein, considering children with dental caries lesions and caries-free ones were selected. In addition, salivary parameters such as salivary flow, pH, buffering capacity, and calcium levels were evaluated. A systematic literature review was carried out in 8 databases. The standardized mean difference (SMD) was measured using inverse variance as a statistical method and random effects as an analysis model, corresponding to a 95% confidence interval (CI). Results. The TAC levels were higher in children affected by dental caries compared to caries-free ones (control group), regardless of age (SMD 2.66; CI 1.33; 3.98), or gender (SMD 0.98; CI 0.56; 1.39). When adjusted for normalized protein, MDA levels were lower in the dental caries group than in the control group (SMD -16.51; CI -29.02; -4.00), and SOD levels were higher in the dental caries group (SMD 5.09; CI 0.01; 10.18). The total protein concentration in saliva of children with dental caries was higher than in the control group, regardless of age (SMD 0.98; CI 0.27; 1.69), or gender (SMD 0.77; CI 0.45; 1.10). The salivary parameters assessed had lower levels in children affected by dental caries (p<0.05). Conclusions. The levels of oxidative stress biomarkers and salivary parameters are altered in saliva of children with dental caries(AU)

Los patrones electroforéticos de proteínas salivales permiten diferenciar los grupos transandino y cisandino de las especies de Rhodnius de Colombia / Salivary proteins electrophoretic patterns enabled differentiating Colombian Rhodnius Trans-Andean and Cis-Andean groups

Introducción. Las especies Rhodnius (Hemiptera: Reduviidae: Triatominae) están conformadas por insectos hematófagos vectores de Trypanosoma cruzi, agente etiológico de la enfermedad de Chagas, y T. rangeli, parásito infectivo pero no patógeno para el vertebrado. El estudio de la diversidad proteica de la saliva de estos insectos permite la obtención de perfiles electroforéticos unidimensionales característicos de algunas especies de triatominos. Sin embargo, el reporte de los patrones electroforéticos de proteínas salivales de las especies de Rhodnius ha sido escaso. Objetivo. Hacer un análisis comparativo de los perfiles electroforéticos unidimensionales de las proteínas salivales de R. colombiensis, R. pallescens, R. pictipes, R. prolixus y R. robustus. Materiales y métodos. Se obtuvieron los perfiles electroforéticos de la saliva de las especies en estudio mediante electroforesis en gel de poliacrilamida con dodecilsulfato sódico (Sodium Dodecyl Sulfate Polyacrylamide Gel Electrophoresis, SDS-PAGE) y se construyó un fenograma mediante el método UPGMA (Unweighted Pair Group Method Using Arithmetic Averages). Resultados. Los perfiles electroforéticos de las proteínas solubles de saliva presentaron bandas en un rango de masa aproximado de 15 a 45 kDa, los cuales permitieron diferenciar las cinco especies estudiadas. El fenograma reveló la existencia de dos grupos principales: uno conformado por los grupos cisandinos Pictipes y Prolixus y otro constituido por el grupo transandino Pallescens. Conclusiones. Existen diferencias en los perfiles electroforéticos de las proteínas salivales entre R. colombiensis, R. pallescens, R. pictipes, R. prolixus y R. robustus, cuya variabilidad permitió construir un fenograma congruente con los grupos del género Rhodnius.

Introduction: Rhodnius (Hemiptera: Reduviidae: Triatominae) species are made up of haematophagous insect vectors for Trypanosoma cruzi (Chagas' disease aetiological agent) and T. rangeli, an infective parasite that is not pathogenic for vertebrate hosts. The study of their salivary protein diversity enables the obtention of characteristic one-dimensional electrophoretic profiles of some triatomine species; however, few reports have dealt with Rhodnius species salivary proteins electrophoretic patterns. Objective: To compare R. colombiensis, R. pallescens, R. pictipes, R. prolixus, and R. robustus' salivary proteins one-dimensional electrophoretic profiles. Materials and methods: SDS-PAGE was used for obtaining electrophoretic profiles of saliva from the species under study. The unweighted pair group method with arithmetic mean (UPGMA) was used for constructing a phenogram. Results: Electrophoretic profiles of soluble saliva had protein bands ranging from 15 to 45 kDa, thereby enabling the five species studied to be differentiated. The phenogram revealed two main groups, one formed by the Pictipes and Prolixus cis-Andean groups and another consisting of the Pallescens trans-Andean group. Conclusion: Differences were revealed regarding R. colombiensis, R. pallescens, R. pictipes, R. prolixus, and R. robustus electrophoretic profiles of salivary proteins; their variability facilitated constructing a phenogram which was taxonomically congruent with the groups from the genus Rhodnius.

Salivary protein characteristics from saliva of carious lesion-free and high caries adults

It has been argued that specific salivary proteins could have a protective effect against caries, but data from the many available studies are rather contradictory. The purpose of this study was to analyze whether there is a relationship between protein concentration, electrophoretic profile and concentration of salivary IgA and the presence or absence of caries in adults. Adults with high caries activity (HC) and without caries lesions (CF), assessed by ICDAS criteria, were asked to provide unstimulated saliva samples. Protein concentration (μg/mL) was determined using the Bradford method. Western blotting was used to detect IgA. Data were compared using Student’s t test at p<0.05. Total protein concentration in CF was higher (50.65±7.5 μg/mL) than in HC individuals (26.80±2.5 μg/mL) (p=0.001). More protein bands were visualized in the gels from CF than the HC group (p=0.001). CF subjects showed higher salivary IgA concentration (11.27±0.5 μg) than HC individuals (1.71±0.2μg) (p=0.001).Salivary composition in high caries experience and cariesfree young adults seems to differ in terms of the type and amount of proteins. Further research is needed to expand these findings.

Se ha descrito que proteínas salivales específicas podrían tener un efecto protector sobre la caries, sin embargo, los datos de los numerosos estudios disponibles son contradictorios. El propósito de este trabajo fue analizar si existe una relación entre la concentración total de proteínas, perfil electroforético y la concentración de IgA salival y la presencia o ausencia de lesiones de caries en adultos. Se obtuvieron muestras de flujo salival no estimulado de adultos con alta actividad de caries (HC) y sin lesiones de caries (CF), evaluados según criterios ICDAS. La concentración total de proteínas (mg / ml) se determinó utilizando el método de Bradford. Para detección de IgA se empleó Western Blot. Los datos se compararon mediante la prueba t student, estableciendo diferencias significativas si p<0,05. La concentración total de proteínas en CF fue mayor (50,65 ± 7,5 mg / ml) que en individuos HC (26,80 ± 2,5 mg / ml) (p=0,001). En los geles, se visualizó un mayor número de bandas de proteínas en CF que en el grupo HC (p=0,001). Los Sujetos CF mostraron mayor concentración de IgA salival (11,27 ± 0,5 μg) que los individuos HC (1,71 ± 0,2 μg) (p=0,001). La composición salival de sujetos adultos jóvenes con alta experiencia y libres de caries, parece ser diferente en función del tipo y la cantidad de proteínas. Se requiere de más investigación para profundizar estos resultados.

Análise microbiológica e imunologica do fluido gengival e proteoma salivar de individuos com Sindrome de Down com doença periodontal / Microbiological and immunological analysis in the gingival crevicular fluid and salivary proteome analysis in individuals with Down syndrome with periodontal disease

O objetivo deste estudo foi avaliar a quantidade de periodontopatógenos e de citocinas inflamatórias no fluido gengival, bem como as proteínas salivares em indivíduos com Síndrome de Down (SD) com Doença Periodontal (DP), comparando-os com indivíduos cromossomicamente normais, antes e 45 dias após o tratamento periodontal não-cirúrgico. Para detectar e quantificar as bactérias (Porphyromonas gingivalis, Tannerella forsythia e Treponema denticola), o fluido gengival foi coletado de 35 indivíduos com DP, sendo 23 indivíduos com SD e 12 não-sindrômicos (controle). Para quantificar as citocinas inflamatórias e as proteínas salivares foram coletados fluido gengival e saliva de 30 indivíduos com DP, sendo 20 indivíduos com SD e 10 não-sindrômicos (controle). Os efeitos do tratamento nos parâmetros clínicos foram positivos para o índice de placa, sangramento à sondagem, profundidade de sondagem e nível de inserção, em ambos os grupos. Porém, a contagem dos periodontopatógenos foi maior nos indivíduos com SD comparados com o grupo controle, antes e 45 dias após o tratamento periodontal. As citocinas Th1, Th2 e Th17 também foram encontradas em maiores quantidades nos indivíduos com SD do que nos controle, mesmo depois do tratamento periodontal. Adicionalmente, maiores quantidades de proteínas salivares com propriedades antimicrobianas, lubrificação, metabolismo, organização celular, resposta imune e transporte foram encontradas em indivíduos com SD depois do tratamento periodontal. Conclui-se que os resultados desta pesquisa podem contribuir para uma compreensão mais aprofundada do comportamento microbiológico, imunológico e do proteoma salivar de indivíduos com SD, e, consequentemente, explicar a alta prevalência e severidade da doença periodontal nesses indivíduos.

The aim of this study was to quantify the periodontopathogens, inflammatory cytokines and salivary proteins in subjects with Down syndrome (DS) and normal subjects, both with periodontal disease (PD), before and 45 days after non-surgical periodontal therapy. To detect and quantify bacteria (Porphyromonas gingivalis, Tannerella forsythia, and Treponema denticola), crevicular gingival fluid (CGF) was collected from 35 individuals with PD, 23 with DS and 12 non-syndromic (control). To quantify the inflammatory cytokines and salivary proteins, CGF and saliva of 30 individuals with PD, 20 with SD and 10 non-syndromic (control) were collected. The effects of the non-surgical periodontal therapy on clinical parameters were positive in both groups. However, the count of periodontopathogens was higher in individuals with DS compared with the control group, before and after periodontal therapy.Th1, Th2 and Th17 cytokines were also found in higher amounts in individuals with DS even after periodontal therapy compared with control patients. Furthermore, higher amounts of salivary proteins with antimicrobial properties, lubrication, metabolism, cellular organization, immune response and transport were quantified in individuals with DS after periodontal therapy. Despite of clinical parameters improvement after non-surgical periodontal therapy in subjects with DS, it is concluded that the results of this study may contribute to a more profound understanding of microbiological and immunological behavior, as well as knowledge of the salivary proteome in individuals with Down syndrome, and also might explain the high prevalence and severity of periodontal disease in these individuals