Molecular mechanism of curcumin on periodontitis: A pharmacological network study.

OBJECTIVE: This study aimed to identify the molecular mechanism of curcumin on periodontitis based on a pharmacological network strategy. METHODS: The potential therapeutic targets of curcumin and differentially expressed genes in periodontitis were identified. Subsequently, we extracted the molecules in common and analyzed them. A metabolic pathway enrichment and gene ontology analysis were performed and the protein-protein interaction network was inferred. These analyses allowed the identification of key proteins. Finally, a molecular docking of the main key proteins was performed with curcumin. RESULTS: Our results showed that 55 genes are differentially expressed in periodontitis and are potential targets of curcumin. In addition, we observed that these genes participate in cell motility and immune response and are related to chemokine receptors (CXCRs) and enzymatic activity, such as arachidonate 5-lipoxygenase (ALOX5). We identified six key proteins, IL1B, CXCL8, CD44, MMP2, EGFR, and ITGAM; molecular docking revealed that these six proteins spontaneously bind to curcumin. CONCLUSION: The results of this study helps us understand the molecular mechanism of curcumin in periodontitis. We propose that curcumin affects proinflammatory cytokines, ALOX5, and cell migration through chemokine receptors and acts on the cell membrane. Additionally, we identified six key proteins that are essential in this mechanism, all of which spontaneously bind to curcumin.

Shared epitope classification methods according to Gregersen and de Vries allow adequate characterization of patients with rheumatoid arthritis in a Colombian population

Introduction: The most important genetic association in rheumatoid arthritis (RA) is presented with some alleles from the HLA-DRB1 gene that encode the shared epitope (SE). Objectives: To apply the SE classification methods of Gregersen, de Vries, Raychaudhuri, Mattey, and Tezenas du Montcel in a group of Colombian patients with RA and determine the most common HLA-DRB1 alleles in the population. Methods: RA diagnosis, genetic study of the HLA-DRB1 region using Luminex technology in 50 RA and 50 healthy subjects. For the classification analysis, Fisher's exact test and chi-squared test were applied. Tables were created to count the RA-related alleles. We used odds ratio to determine the risk between the presence of the shared epitope (SE) and anti-cyclic citrullinated peptides (Anti-CCP). Results: Gregersen and de Vries methods were suitable for the characterization of RA in this population (p = .006). The most prevalent HLA-DRB1 alleles in the RA group were 14:02,04:04, 08:02,04:05, and 10:01. High frequencies of the 07:01, 03:01,13:02,01:02, and 12:01 HLA-DRB1 alleles were found in the healthy population. HLA-DRB1 alleles with similar distribution in both populations were 04:07, 15:01, 11:01, 16:02, and 01:01. A high frequency of SE + was observed in Anti-CCP + individuals (63.15%); however, this was not statistically significant [OR2.4 (.63-9.01); p = .19]. Conclusion: The SE classification methods of Gregersen and de Vries were adequate in characterizing RA in a Colombian population group. An equivalence of 100% was verified between the susceptibility alleles defined by de Vries and the alleles assigned as SE according to Gregersen.

Introducción: La asociación genética más importante en artritis reumatoide (AR) se presenta con algunos alelos del gen HLA DRB1 que codifican el epítope compartido (EC). Objetivos: Aplicar los métodos de clasificación de EC de Gregersen et al., de Vries et al., Raychaudhuri et al., Mattey et al., y Tezenas du Montcel et al., en un grupo de pacientes colombianos con AR, y determinar los alelos HLA DRB1 más frecuentes en esta población. Métodos: Diagnóstico para AR, estudio genético de la región HLA DRB1 por tecnología Luminex® de 50 sujetos AR y 50 sanos. Para análisis comparativos de clasificaciones EC, se aplicaron las pruebas test exacto de Fisher y Chi-cuadrado y se realizaron tablas de conteos para los alelos relacionados con AR. Se estimó la razón de odds para determinar el riesgo entre la presencia de EC y los anticuerpos antipéptidos cíclicos citrulinados (anti-PCC). Resultados: Los métodos de Gregersen et al. y de Vries et al. fueron adecuados para la caracterización de AR en esta población (p = 0,006). Los alelos HLA DRB1 más prevalentes en el grupo AR fueron 14:02, 04:04, 08:02, 04:05 y 10:01. Se encontraron altas frecuencias de los alelos HLA DRB1 07:01, 03:01,13:02, 01:02 y 12:01 en población sana. Alelos HLA DRB1 con distribución similar en ambas poblaciones fueron: 04:07, 15:01, 11:01, 16:02 y 01:01. Se observó alta frecuencia de individuos EC+ en el grupo AR anti-PCC+ (63,15%); no obstante, sin asociación estadística (OR: 2,4 [0,63-9,01]; p = 0,19). Conclusión: Los métodos de clasificación para EC de Gregersen et al. y de Vries et al. fueron adecuados caracterizando AR en un grupo de población colombiana. Se corroboró equivalencia del 100% entre los alelos de susceptibilidad definidos por de Vries y los alelos asignados como EC según Gregersen et al.

Relación entre Porphyromonas gingivalis y diabetes mellitus tipo 2: revisión sistemática exploratoria / Relationship between Porphyromonas gingivalis and Type 2 Diabetes Mellitus: Scoping review

Objetivo: analizar la relación entre Porphyromonas gingivalis y diabetes mellitus tipo 2, mediante una revisión sistemática exploratoria de la literatura científica publicada entre los años 2000 y 2019. Métodos: se utilizaron los siguientes términos MeSH: Porphyromonas gingivalis, diabetes mellitus type 2, periodontal disease, non insulin dependent diabetes. Se obtuvieron 346 resultados, de los cuales se seleccionaron 41 por título, se excluyeron 11 posterior a la lectura del abstract e introducción y 19 después de la lectura del texto completo. Finalmente, se incluyeron 11 artículos. Resultados: el lipopolisacárido de Porphyromonas gingivalis y su fimbria tipo II se relacionan con una mayor producción de citoquinas proinflamatorias como IL-6 y TNF-α, las cuales afectan las vías de señalización de la glucosa y se relacionan con insulinoresistencia. La dipeptidil peptidasa 4 de Porphyromonas gingivalis puede participar en la degradación de incretinas, lo cual afecta la producción de insulina en el huésped y promueve estados de hiperglicemia. El interactoma de Porphyromonas gingivalis puede superponerse con genes involucrados en resistencia a la insulina y diabetes mellitus tipo 2. Conclusión: según la evidencia científica publicada existen factores de virulencia y mecanismos por los cuales la Porphyromonas gingivalis influye en el desarrollo de insulinorresistencia y diabetes mellitus tipo 2.

Objective: To analyze the relationship between Porphyromonas gingivalis and Diabetes Mellitus Type 2 by reviewing the scientific literature published between 2000 and 2019. Methods: The following MeSH terms were used: Porphyromonas gingivalis, Diabetes Mellitus type 2, periodontal disease, non-insulin dependent diabetes. We obtained 346 results, of which 41 were selected by title, 11 were excluded after reading the abstract and introduction and 19 after reading the full text. Finally, 11 articles were included. Results: Porphyromonas gingivalis lipopolysaccharide and its type II fimbria are associated with increased production of proinflammatory cytokines such as IL-6 and TNF-α, which affect glucose signaling pathways and are related to insulin resistance. Porphyromonas gingivalis dipeptidyl peptidase 4 (PgDPP4) may participate in incretin degradation which affects host insulin production and promotes hyperglycemic states. The Porphyromonas gingivalis interactome may overlap with genes involved in insulin resistance and type 2 diabetes mellitus. Conclusion: According to published scientific evidence, there are virulence factors and mechanisms by which Porphyromonas gingivalis influences the development of insulin resistance and type 2 Diabetes Mellitus.