PYCARD gene polymorphisms and susceptibility to periodontal and coronary heart diseases.

Numerous studies have established a link between gene variants within the inflammasome complex and the incidence of periodontitis and cardiovascular illness across various ethnic groups. This study investigated the association between PYCARD gene polymorphism and susceptibility to periodontal disease and coronary heart disease (CHD) and their correlation with clinical periodontal indices. A total of 120 participants were enrolled, categorized into four groups: 30 healthy controls (C), 30 patients with generalized periodontitis (P), 30 patients with atherosclerotic CHD but clinically healthy periodontium (AS-C), and 30 patients with both atherosclerotic CHD and generalized periodontitis (AS-P). We recorded demographic data, collected blood samples, and measured periodontal indices, including plaque index, clinical attachment loss, bleeding on probing, and pocket depth. The genomic variant of the PYCARD gene was analyzed using a conventional polymerase reaction. A significant prevalence of T and G allele mutations and a higher distribution of CT and TT genotypes in PYCARD C/T (rs8056505) and the AG genotype in PYCARD A/G (rs372507365) were observed in groups P, AS-P, and AS-C. These single nucleotide polymorphisms (SNPs) were also positively correlated with the severity of clinical periodontitis indices. Our findings suggest that the increased frequency of T and G alleles and the distribution of CT, TT, and AG genotypes in PYCARD SNPs are significantly associated with an elevated risk for periodontal disease and CHD. These SNPs may participate in the pathogenesis of these conditions. The study reinforces the potential role of these genetic markers as risk factors for both diseases in the Iraqi population.

MicroRNA-155 (miR-155) as an accurate biomarker of periodontal status and coronary heart disease severity: a case-control study.

BACKGROUND: Increasing evidence supports associations between periodontal disease and coronary heart disease (CHD). This case-control study evaluated whether inflammatory regulator, microRNA-155 (miR-155), could be utilised as a biomarker of periodontitis and/or CHD. METHODS: Of 120 participants, 30 patients had clinically healthy periodontium (controls, C), 30 patients had generalized periodontitis (P), 30 patients had CHD and clinically healthy periodontium (AS-C); and 30 patients had CHD with generalized periodontitis (AS-P). Patient demographic and periodontal characteristics (plaque index, bleeding on probing, probing pocket depth and clinical attachment loss), were collected. Patient whole blood and saliva levels of miR-155 and pro-inflammatory cytokine (interleukin-1ß), were quantified by quantitative real time polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA). One-way ANOVA with post-hoc Tukey test was used to determine differences among the four groups. Chi Square test was used for participant gender comparisons. Pearson correlation tests and multiple linear regression analyses were used to assess associations between the demographic and clinical variables analysed, versus IL-1ß and miR-155 levels. miR-155 and IL-1ß accuracy in differentiating healthy versus other patient groups were analysed using receiver operating characteristic (ROC) curves, by calculating area under the curve (AUC) values and sensitivity and specificity cut-off points using Youden's index. Statistical tests of sensitivity and specificity were conducted using the McNemar test. RESULTS: Whole blood miR-155 levels were elevated in periodontitis/non-periodontitis patients with CHD (AS-P, AS-C), and periodontitis patients alone (P) (p < 0.001). Receiver operating characteristic (ROC) and area under the curve (AUC) analyses confirmed miR-155 accuracy in discriminating P, AS-C and AS-P groups (AUC 0.6861-0.9944, p < 0.0001-0.05), coupled with high sensitivity (76.7-100.0%), specificity (53.3-96.7%) and cut-off points (> 0.955- > 2.915 a.u.; p < 0.0001). miR-155 levels further distinguished between CHD (AS-C, AS-P) and periodontitis (P) patients (AUC ≥ 0.8378, sensitivity ≥ 88.7%, specificity ≥ 73.3%, cut-off > 2.82 a.u; p < 0.0001), and between AS-C and AS-P patients (AUC 0.7578, sensitivity 80.0%, specificity 50.0%, cut-off > 7.065 a.u; p < 0.001). Subsequent analyses identified positive correlations between miR-155 and the various patient demographics, salivary interleukin-1ß and periodontal parameters assessed. CONCLUSIONS: This study advocates miR-155 as an accurate diagnostic/prognostic biomarker of periodontitis and/or CHD severity, thereby improving detection and treatment for both conditions.

Association Between AIM2 and Pycard Genes Polymorphisms and Susceptibility to Periodontitis with Coronary Heart Disease.

Background: Numerous genetic variations in inflammasome components are linked to prevalent disorders in the general population, including periodontitis and cardiovascular illness. Polymorphisms in the genes play a critical in the initiation and development of inflammatory diseases. The limited study on AIM2 gene variation associated with inflammatory disease and no study of PYCARD gene variation associated with inflammatory disease. Objective: This case-control study was to examine the association between the single nucleotide polymorphism of AIM2 and Pycard genes with susceptibility to periodontitis with and without coronary heart disease, to determine interleuken-18 and gasdermin D levels in the saliva of periodontitis with and without coronary heart disease patients, as well as their correlation with salivary interleuken-18 and gasdermin D levels and clinical periodontal parameters. Methods: The present study recruited 120 participants: 30 were healthy subjects (control, C), 30 had generalized periodontitis (P), 30 had atherosclerosis coronary heart disease with clinically healthy periodontium (AS-C), and 30 had atherosclerosis coronary heart disease with generalized periodontitis (AS-P). All individuals' demographic data recorded, saliva and blood samples collected, then periodontal characteristics were detailed. These parameters include plaque index, bleeding on probing, probing pocket depth, and clinical attachment loss. AIM2 and Pycard gene polymorphisms were analyzed by polymerase chain reaction assay, electrophoresis and sequencing. An enzyme-linked immunosorbent assay (ELISA) was conducted to determine the level of interleuken-18 and gasdermin D in their saliva. Results: The study result of high frequency (T) in single-nucleotide polymorphisms. The high genotypes distribution of GT and TT genotypes in the AIM2 gene and the CT and TT genotypes in the Pycard gene were detected in the periodontitis, atherosclerosis coronary heart disease with healthy periodontium and atherosclerosis coronary heart disease with generalized periodontitis groups as compared to control group. Elevation of salivary interleuken-18 and gasdermin D levels in three patients' groups compared to healthy controls. Both these single-nucleotide polymorphisms also significantly correlated with higher salivary interleuken-18 and gasdermin D levels and worse clinical indices of periodontitis. Conclusion: Single-nucleotide polymorphisms in the AIM2 and Pycard genes are associated with an increased risk of developing periodontitis with and/or without coronary heart disease. Elevation of salivary interleuken-18 and gasdermin D levels associated and impacted on periodontitis with and/or without coronary heart disease. These single-nucleotide polymorphisms may provide evidence for a genetic role in the pathogenesis of periodontitis with and without atherosclerosis coronary heart disease.

Assessing the level and diagnostic accuracy of osteopontin and oral health status in periodontitis patients with/without Type-2 Diabetes Mellitus / Avaliação do nível e precisão do diagnóstico de Osteopontina e estado de saúde bucal em pacientes com periodontite com/sem Diabetes Mellitus tipo 2

Objective: Investigating osteopontin (OPN) level in gingival crevicular fluid (GCF) of patients affected by periodontitis with or without Type-2 diabetes mellitus (T2DM). The aim of this study is to explore the possibility of OPN to differentiate between periodontal health and disease. Material and Methods: A total number of 36 participants seeking periodontal treatment were recruited in this pilot study and divided into three study groups. Periodontitis [systemically healthy participants with periodontitis (probing pocket depth) PPD (probing pocket depth) ≥ 4mm], periodontitis and poorly controlled type 2 diabetes mellitus (), and control (systemically and periodontally healthy periodontium) groups. Plaque index (PI), gingival index (GI) and PPD were examined. OPN level was measured in the GCF and analysed, using Enzyme-Linked Immunosorbent assay. Results: PI and GI were significantly higher in T2DM with periodontitis compared to periodontitis and control groups. Both periodontitis and P-T2DM groups showed significant increase in the OPN levels compared to control group (p<0.001). PPD showed the only significant positive association with OPN (p<0.001) compared to other clinical parameters. The receiver operating characteristics curve analysis demonstrated that OPN had higher area under the curve value (AUC: 0.95) in periodontitis compared to P-T2DM patients (AUC: 0.86). Conclusion: In periodontitis groups, clinical parameters were equally deteriorated together with significant increase in the expression of OPN compared to control. Furthermore, GCF levels of OPN were sensitive and specific enough to discriminate between health and periodontitis even with T2DM. This could introduce OPN to be as a candidate diagnostic biomarker of periodontal disease. (AU)

Objetivo: Investigar o nível de osteopontina (OPN) no fluido gengival crevicular (GCF) de pacientes com periodontite com ou sem diabetes mellitus tipo 2 (T2DM). O objetivo deste estudo foi explorar a possibilidade da OPN diferenciar entre saúde e doença periodontal. Material e Métodos: No total, para este estudo piloto foram recrutados 36 participantes que estavam em busca de tratamento periodontal e divididos em três grupos de estudo: grupos periodontite [participantes sistemicamente saudáveis com periodontite (profundidade de sondagem) PPD ≥ 4 mm], grupo periodontite e Diabetes Mellitus tipo 2 mal controlada (P-T2DM) e grupo controle (saudáveis sistemicamente e periodontalmente). Índice de placa (PI), índice gengival (GI) e PPD foram examinados. O nível de OPN foi medido no GCF e analisado usando o ensaio ELISA (Enzyme-Linked Immuno Sorbent Assay). Resultados: PI e GI foram significativamente maiores no T2DM com periodontite em comparação aos grupos com periodontite e controle. Os grupos com periodontite e P-T2DM apresentaram aumento significativo nos níveis de OPN em comparação ao grupo controle (p <0,001). PPD mostrou a única associação positiva significativa com OPN (p <0,001) em comparação com outros parâmetros clínicos. A análise da curva de características operacionais do receptor demonstrou que OPN teve maior área sob o valor da curva (AUC: 0,95) na periodontite em comparação com pacientes com P-T2DM (AUC: 0,86). Conclusão: Nos grupos com periodontite, os parâmetros clínicos foram igualmente deteriorados juntamente com aumento significativo na expressão de OPN em comparação com o grupo controle. Além disso, os níveis de OPN no GCF foram sensíveis e específicos o suficiente para discernir entre saúde e periodontite, mesmo com T2DM. Isso poderia apresentar a OPN como um candidato a biomarcador diagnóstico de doença periodontal.(AU)

Effects of high glucose conditions on the expansion and differentiation capabilities of mesenchymal stromal cells derived from rat endosteal niche.

BACKGROUND: Mesenchymal stromal cells in the endosteal niche lining compact bone (CB-MSCs) represent a heterogeneous population, all of which contribute to bone repair and remodelling. Hyperglycaemia associated with type 2 diabetes mellitus (T2DM) can delay and impair the bone healing process. Therefore, this study investigated the influences of high (25 mM) glucose conditions on CB-MSC populations isolated from male Wistar rats, versus normal (5.5 mM) glucose conditions; in terms of proliferation (population doublings, PDs), senescence characteristics, stem cell marker expression, colony forming efficiencies (CFEs); and osteogenic/adipogenic differentiation, following extended culture in vitro. RESULTS: CB-MSCs under both normoglycaemic and hyperglycaemic conditions demonstrated similar morphologies and rapid exponential growth to >300PDs, although high glucose conditions promoted more rapid and persistent proliferation beyond ~50PDs, with few indications of senescence. Limited senescence was confirmed by minimal SA-ß-galactosidase staining, low senescence marker (p53, p21waf1, p16INK4a) expression and positive telomere maintenance marker (rTERT, TR) expression. However, telomere lengths varied throughout culture expansion, with hyperglycaemia significantly reducing telomere lengths at PD50 and PD200. Furthermore, CB-MSCs expanded in normal and high glucose conditions remained non-transformed, exhibiting similar MSC (CD73/CD90/CD105), multipotency (CD146) and embryonic (Slug, Snail) markers throughout extended culture, but negligible hematopoietic (CD34/CD45) or pluripotency (Nanog, Oct4) markers. Hyperglycaemia significantly increased CFEs at PD50 and PD100, which decreased at PD200. CB-MSC osteogenic differentiation was also inhibited by hyperglycaemia at PD15, PD100 and PD200, but not at PD50. Hyperglycaemia inhibited CB-MSC adipogenic differentiation to a lesser extent at PD15 and PD50, with reduced adipogenesis overall at PD100 and PD200. CONCLUSION: This study demonstrates the limited negative impact of hyperglycaemia on the proliferative and stem cell characteristics of heterogeneous CB-MSC populations, although minor sub-population(s) appear more susceptible to these conditions leading to impaired osteogenic/adipogenic differentiation capabilities. Such findings potentially highlight the impact of hyperglycaemia on CB-MSC bone repair capabilities in situ.