Mechanism of action of Coptidis Rhizome in treating periodontitis based on network pharmacology and in vitro validation.

OBJECTIVE: Explore the therapeutic mechanism of Coptidis Rhizome (CR) in periodontitis using network pharmacology, and validate it through molecular docking and in vitro experiments. METHODS: Screened potential active components and target genes of CR from TCMSP and Swiss databases. Identified periodontitis-related target genes using GeneCards. Found common target genes using Venny. Conducted GO and KEGG pathway analysis. Performed molecular docking and in vitro experiments using Berberine, the main active component of CR, on lymphocytes from healthy and periodontitis patients. Assessed effects on inflammatory factors using CCK-8, flow cytometry, and ELISA. RESULTS: Fourteen active components and 291 targets of CR were identified. 30 intersecting target genes with periodontitis were found. GO and KEGG analysis revealed oxidative stress response and IL-17 signaling pathway as key mechanisms. Molecular docking showed strong binding of Berberine with ALOX5, AKT1, NOS2, and TNF. In vitro experiments have demonstrated the ability of berberine to inhibit the expression of Th17 + and other immune related cells in LPS stimulated lymphocytes, and reduce the secretion of IL-6, IL-8, and IL-17. CONCLUSION: CR treats periodontitis through a multi-component, multi-target, and multi-pathway approach. Berberine, its key component, acts through the IL-17 signaling pathway to exert anti-inflammatory effects.

Mean platelet volume is associated with periodontitis: a cross-sectional study.

BACKGROUND: It is uncertain if mean platelet volume and periodontitis are related. The objective of this study was to examine the association between levels of mean platelet volume and moderate/severe periodontitis in adult persons who inhabit the U.S. METHODS: We screened 6,809 people from the National Health and Nutrition Examination Survey (NHANES 2009-2012). Mean platelet volume was measured in the Mobile Examination Centers (MECs) using the Beckman Coulter analyzer. The category of periodontitis was defined by the CDC/AAP using clinical periodontal parameters. Multiple logistic regression models were employed to examine the distribution for covariate differences across the various independent groups. Four models were employed to examine the relationship between mean platelet volume level and periodontitis. Smoothed curve fitting was utilized to confirm the linearity of the relationships. To determine the impact of factors on the connection between MPV and periodontitis, subgroup analysis and interaction testing were utilized. RESULTS: Results from the multiple logistic regression analysis indicate a significant association between moderate/severe periodontitis and the mean platelet level, even after considering any potential confounding variables (OR = 1.090, 95% CI: 1.019-1.166, P-value = 0.01211). Additionally, those in the upper tertile of mean platelet volume levels had a 21.6% higher probability of developing periodontitis when compared with those in the least tertile of mean platelet levels (OR = 1.216, 95% CI:1.052-1.406, P-value = 0.00816). Moreover, it showed a positive correlation between mean platelet volume (MPV) and moderate/severe periodontitis. Subgroup analyses indicated a positive association between the level of mean platelet volume and moderate/severe periodontitis among individuals who were under 60 years of age, had low income, were obese, never smoked, were heavy drinkers, had hypertension, and had no cardiovascular disease (p < 0.05). However, none of the subgroups exhibited significant interactions (p for interaction > 0.05). CONCLUSION: A correlation has been found between mean platelet volume levels and periodontal disease in individuals residing in the United States.

Investigating the causal relationship between human blood/urine metabolites and periodontal disease using two-sample Mendelian randomization.

Background and Aims: The aim is to investigate the cause-and-effect connection between metabolites found in blood/urine and the likelihood of developing periodontal disease (PD) through the utilization of a two-sample Mendelian randomization (MR) method. Methods: Using an inverse variance weighted (IVW) method and two additional two-sample MR models, we examined the relationship between blood/urine metabolites and PD by analyzing data from a comprehensive metabolome-based genome-wide association study and the Genome-Wide Association Studies (GWAS) of PD. To assess the consistency and dependability of the findings, diversity, cross-effects, and sensitivity analyses were conducted. Results: Out of the 35 metabolites found in blood and urine, a total of eight metabolites (C-reactive protein, Potassium in urine, Urea, Cystatin C, Non-albumin protein, Creatinine, estimated Glomerular Filtration Rate, and Phosphate) displayed a possible causal connection with the risk of dental caries/PD using the inverse variance weighted (IVW) method (p < 0.05). This includes five metabolites in the blood and three in the urine. No metabolites were statistically significant in IVW MR models (p < 3.68 × 10- 4). Even after conducting sensitivity analysis with the leave-one-out method and removing the confounding instrumental variables, the impact of these factors on dental caries/PD remained significant. Conclusion: Based on the available evidence, it is not possible to establish a significant causal link between the 35 blood metabolites and the likelihood of developing dental caries and PD.

The associations of two novel inflammation indexes, systemic immune-inflammation index (SII) and system inflammation response index (SIRI), with periodontitis: evidence from NHANES 2009-2014.

OBJECTIVES: The research's goal is to look for any potential relationships between the systemic immune-inflammation index (SII) and the system inflammation response index (SIRI), along with inflammation indicators and the likelihood of periodontitis. METHODS: Ten thousand two hundred eighty-two individuals in sum were determined to be eligible for this cross-sectional study from the National Health and Nutrition Examination Survey (NHANES) between 2009 and 2014. Multiple logistic regression, generalized additive model, smooth curve fitting, subgroup analysis, and interaction tests were done for analyzing the association between periodontitis and SII, SIRI, and other inflammatory indicators. RESULTS: The analysis, adjusted for population weighting, revealed that individuals with moderate/severe periodontitis had SII levels of 545.46 (95% CI (529.10, 561.82), P = 0.0044) and SIRI levels of 1.33 (95% CI (1.29, 1.37), P < 0.0001). In a fully adjusted multivariate logistic regression model, SII was not sensibly associated with moderate/severe periodontitis among the continuous and quartile Q1-Q4 groups (OR = 0.97, 95% CI (0.91, 1.02)). The continuous variable of SIRI (OR = 1.11, 95% CI (1.06, 1.17)) and the quartile Q4 group (OR = 1.58, 95% CI (1.28, 1.94)) had a deemed significant positive association with moderate to severe periodontitis. In addition, other inflammatory indicators, especially NLR, PPN, PLR, MLR, PC, NC, and MC were observed to be notably involved moderate/severe periodontist in this research. CONCLUSION: We explored the association between periodontitis and two novel comprehensive markers of inflammation (SII and SIRI). CLINICAL RELEVANCE: These inflammatory markers are expected to serve as tools to assist clinicians in diagnosing periodontitis.

The association between sedentary behavior and obstructive sleep apnea: a cross-sectional study from the NHANES (2007-2008 to 2015-2020).

BACKGROUND: Sedentary behavior (SB) may contribute to obesity and lower extremity fluid retention, which may favor the development of obstructive sleep apnea (OSA). However, linking sedentary behavior to OSA is unclear. The purpose of this study was to determine if there is an association between SB and OSA. METHODS: Three typical questions in the NHANES questionnaire(①The frequency of feeling excessively sleepy per month. ②The frequency of gasping, snorting or stopping breathing per week. ③The frequency of snoring per week.) have been used for the assessment of OSA. A physical activity questionnaire(On a typical day, the amount of time you spend sitting or reclining.) was used to assess SB. This secondary analysis included National Health and Nutrition Examination Survey (NHANES) participants (unweighted = 20,115). Weighted sample and multiple logistic regression complex sample analysis techniques were used in this study. RESULTS: After adjustment for confounders, participants with SB(> 8 h/d) had a higher risk of OSA compared to SB(< 4 h/d). Stratified analysis by gender showed that there was no significant association of SB and OSA in men. However, in women, with SB(< 4 h/d) as the reference, participants with(≥ 4 h/d) had an increased risk of OSA. By age-stratified analysis, the association of SB with OSA was stronger among older participants. CONCLUSION: Analysis in this study showed a positive association between SB and OSA, more pronounced in women and participants older than 60 years old.

Exposure to heavy metal elements may significantly increase serum prostate-specific antigen levels with overdosed dietary zinc.

BACKGROUND: Serum prostate-specific antigen (PSA) is a primary metric for diagnosis and prognosis of prostate cancer (PCa). Exposure to heavy metals, such as lead, cadmium, mercury, and zinc can impact PSA levels in PCa patients. However, it is unclear whether this effect also occurs in men without PCa, which may lead to the overdiagnosis of PCa. METHOD: Data on a total of 5089 American men who had never been diagnosed with PCa were obtained from the National Health and Nutrition Examination Survey performed from 2003-2010. The relationship between serum PSA levels (dependent variable) and concentrations of lead (µmol/L), cadmium (nmol/L), and mercury (µmol/L) were investigated with dietary zinc intake being used as a potential modifier or covariate in a weighted linear regression model and a generalized additive model. A series of bootstrapping analyses were performed to evaluate sensitivity and specificity using these models. RESULTS: Regression analyses suggested that, in general, lead, cadmium, or mercury did not show an association with PSA levels, which was consistent with the results of the bootstrapping analyses. However, in a subgroup of participants with a high level of dietary zinc intake (≥14.12 mg/day), a significant positive association between cadmium and serum PSA was identified (1.06, 95% CI, P = 0.0268, P for interaction=0.0249). CONCLUSIONS: With high-level zinc intake, serum PSA levels may rise in PCa-free men as the exposure to cadmium increases, leading to a potential risk of an overdiagnosis of PCa and unnecessary treatment. Therefore, environmental variables should be factored in the current diagnostic model for PCa that is solely based on PSA measurements. Different criteria for PSA screening are necessary based on geographical variables. Further investigations are needed to uncover the biological and biochemical relationship between zinc, cadmium, and serum PSA levels to more precisely diagnose PCa.

The peripheral immune cell counts and mouth ulcers: A two-sample Mendelian randomization study.

Objective: This study explored the causal association of peripheral immune cell counts with mouth ulcers (MUs) by two-sample Mendelian Randomization. Design: The counts of 12 circulating immune cell types (leukocytes, lymphocytes, monocytes, eosinophils, neutrophils, basophils, CD4+ cells, CD8+ cells, unswitched memory B cells, NK cells, B cells and a derived ratio (CD4+/CD8+)) were determined as the exposure. MUs were the outcome. The analysis was conducted mostly using the inverse-variance weighted (IVW) approach. MR Egger, weighted median, weighted mode and simple mode were used to detect the horizontal pleiotropy. Results: The IVW results for leukocytes and lymphocyte counts were OR = 0.93, 95 % CI = 0.88-0.98, p = 0.0115 and OR = 0.91, 95 % CI: 0.84-0.98, p = 0.0150, respectively. The Wald ratio result for CD4+ cell and CD8+ cell counts were OR = 0.70, 95 % CI: 0.65-0.75, p = 1.05 × 10-20 and OR = 1.25, 95 % CI: 1.19-1.31, p = 9.99 × 10-21, respectively. Conclusions: This study supports a causal effect of peripheral immune cell counts on MUs. Higher leukocyte, lymphocyte and CD4+ cell counts can protect against MUs, but higher CD8+ cell counts enhance the risk of MUs. This finding confirms host immune factors play a crucial role in the aetiology of MUs.

Association between life's essential 8 and periodontitis: a population-based study.

BACKGROUND: The American Heart Association has developed a novel cardiovascular health indicator called Life's Essential 8 (LE8). However, no one has reported using LE8 to assess periodontitis. This study aimed to investigate the association between LE8 and periodontitis in American adults. METHODS: Data from the National Health and Nutrition Examination Survey (NHANES) from 2009 to 2014 were used for this investigation. LE8 was the independent variable, and it is divided into three grades: high, moderate, and low. Periodontitis was the dependent variable, and the classification of periodontitis was based on the criteria of Eke in 2012. Multivariable logistic regression models were used to explore the relationship between LE8 and periodontitis. RESULTS: A total of 9,039 participants with an average age of 52.16 ± 14.21 years were enrolled in this study, of whom 48.29% were male and 51.71% were female. The mean and standard deviation of LE8 was 66.29 ± 14.57, and the prevalence of periodontitis was 50.48% overall. The LE8 score and periodontitis in the fully adjusted logistic regression model showed a negative correlation (OR = 0.98; 95% CI, 0.98-0.99, p < 0.001). This result persisted when Life's Essential 8 was categorized into low, moderate, and high groups. Compared with those in the lowest group, those in the highest LE8 group had a 47% decreased risk of periodontitis (OR = 0.53; 95% CI, 0.46-0.66, P < 0.001). CONCLUSIONS: This cross-sectional investigation revealed a negative relationship between the LE8 score and the likelihood of periodontitis.

Understanding the consequences of leisure sedentary behavior on periodontitis: A two-step, multivariate Mendelian randomization study.

Background: The relationship between leisure sedentary behavior (LSB) and periodontitis risk remains unclear in terms of causality and the potential mediating effects of intermediate factors. Materials and methods: Using the aggregate data of several large-scale genetic association studies from participants of European descent, we conducted a univariate, two-step, and multivariate Mendelian random (MR) analysis to infer the overall effect of LSB on periodontitis, and quantified the intermediary proportion of intermediary traits such as smoking. Results: Our findings indicated that per 1-SD increase (1.87 h) in leisure screen time (LST), there was a 23 % increase in the risk of periodontitis. [odds ratios (95 % CI) = 1.23 (1.04-1.44), p = 0.013]. Smoking was found to partially mediate the overall causal effect of LST on periodontitis, with a mediation rate of 20.7 % (95 % CI: 4.9%-35.5 %). Multivariate MR analysis demonstrated that the causal effect of LST on periodontitis was weakened when adjusting for smoking, resulting in an odds ratio of 1.19 (95 % CI: 1.01-1.39, p = 0.049) for each 1 standard deviation increase in exposure. Conclusion: The study provides evidence of a potential causal relationship between LSB characterized by LST and periodontitis, thereby further supporting the notion that reducing LSB is beneficial for health. Furthermore, it confirms the role of smoking as a mediator in this process, suggesting that inhibiting smoking behavior among individuals with long-term LSB may serve as a strategy to mitigate the risk of periodontitis.

Association of Sleep Duration with Tooth Loss and Periodontitis: Insights from the National Health and Nutrition Examination Surveys (2005-2020).

OBJECTIVE: Sleep disorders such as insomnia, apnea, and restless leg syndrome can negatively affect a person's overall health and may cause hypertension, heart failure, and coronary heart disease. Likewise, periodontitis, a gum disease, can lead to both physical and psychological health issues, exerting a considerable effect on one's overall well-being-periodontitis stands as a primary cause of tooth loss. Nevertheless, there has been insufficient research on the correlation between the amount of sleep individuals get and the occurrence of periodontitis/tooth loss among Americans. Therefore, this study aimed to assess the influence of sleep length on periodontitis in the American population. METHODS: Periodontitis severity was classified (none, mild, moderate, and severe) using American Periodontal Association criteria. Sleep duration was assessed by self-reported data and categorized into three groups (deficient, adequate, and excessive). Tooth loss was assessed by the oral examination. To establish a connection between the duration of sleep and periodontitis/tooth loss, a weighted multivariable logistic regression analysis was employed. A GAM analysis and smooth curve fitting assessment were conducted to identify non-linear relationships. Subgroup, interaction, and mediation analyses were also performed. RESULTS: The prevalence of tooth loss was significantly high, affecting 96.4% of the individuals, whereas 46.6% of the study sample experienced moderate to severe periodontitis. The average age of participants was 52.7 years. After adjusting for potential confounding factors, the analysis of weighted multivariable logistic regression revealed a significant association between sleep insufficiency and moderate/severe periodontitis (OR 1.15, 95% CI 1.01-1.30, P = 0.0298), as well as tooth loss (OR 1.16, 95% CI 1.01-1.33, P = 0.0371). Additionally, the research showed a correlation between the length of sleep and periodontitis that followed a U-shaped pattern. In addition, the analysis of mediation revealed that high blood pressure explained 7.0% (95% CI 4.0% to 12.9%; P < 0.0001) of the link between the amount of sleep and the likelihood of losing teeth. CONCLUSION: Sleep duration was independently correlated with moderate/severe periodontitis/tooth loss and had a non-linear relationship.

Causal relationship between psychiatric traits and temporomandibular disorders: a bidirectional two-sample Mendelian randomization study.

OBJECTIVES: This study was to investigate the causal relationship between temporomandibular disorders (TMD) and psychiatric disorders by Mendelian randomization (MR) analysis. MATERIALS AND METHODS: A two-sample bidirectional MR analysis was adopted to systematically explore the causal relationship between TMD and eight psychiatric traits, including anxiety disorder (AD), panic disorder (PD), major depressive disorder (MDD), neuroticism, attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), bipolar disorder (BIP), and schizophrenia (SCZ). Inverse variance weighted (IVW), weighted median, and MR-Egger regression were used in my study. Furthermore, we also performed three sensitivity analyses to illustrate the reliability of the analysis. RESULTS: Two psychiatric traits have risk effects on TMD: PD (OR = 1.118, 95% CI: 1.047-1.194, P = 8.161 × 10-4, MDD (OR = 1.961, 95% CI: 1.450-2.653, P = 1.230 × 10-5). Despite not surpassing the strict Bonferroni correction applied (P > 0.00625), we could think that there was a suggestive causal effect of neuroticism and SCZ increasing the risk of TMD. On the reverse MR analysis, we found no significant evidence of causal effects of TMD on these psychiatric traits. Except for heterogeneity in the causal analysis for SCZ on TMD, no heterogeneity and horizontal pleiotropy were detected in the other analyses. CONCLUSIONS: Our two-sample MR study has provided further evidence of PD and MDD being related to a higher risk of TMD. CLINICAL RELEVANCE: These findings highlight the importance of closely monitoring mental traits during future TMD treatments to prevent an increased risk of TMD.

Association between muscle quality index and periodontal disease among American adults aged ≥ 30 years: a cross-sectional study and mediation analysis.

OBJECTIVE: The muscle quality index (MQI) is a measurement of muscle quality that is directly related to overall health. There has been little study on the relationship between the muscle quality index and periodontitis in American people beyond 30 years. Therefore, this study aimed to explore the link between periodontitis and Muscle quality index (MQI) in older Americans. METHODS: Three thousand two hundred fifty-eight individuals (aged 30 to 59) who participated in the National Health and Nutrition Examination Survey (NHANES) 2011-2014 were considered eligible for the cross-sectional investigation. A hand dynamometer was used to determine the handgrip strength (HGS). Dual-energy X-ray absorptiometry was employed to calculate ASM (DXA). MQIArm was calculated by dividing the dominant hand's HGS by the dominant arm's ASM (in kg/kg). MQIApp was calculated by dividing the dominant hand's HGS by the ASM (in kg/kg). MQItotal was calculated by dividing the sum of the dominant and non-dominant hands by the ASM (in kg/kg). To investigate the link between muscle quality index and periodontal disease, the weighted multivariable logistic regression models were used. Using generalized additive models, it was determined if a nonlinear connection existed. Then, we developed a two-piece linear regression model and calculated the inflection point using a recursive approach. A mediation study was performed to determine how much of the impact of MQItotal on periodontitis was mediated by potential variables. RESULTS: Three thousand two hundred fifty-eight participants from the United States were enrolled. The OR (95% CI) for the relationship between MQItotal and periodontitis in the regression model with fully adjusted variables was 0.69 (0.53-0.91), for the connection between MQIArm and periodontitis was 0.90 (0.84-0.97), and for the association between MQIApp and periodontitis was 0.49 (0.30-0.80). MQItotal and periodontitis were shown to have a J-shaped relationship with a change point of 3.64. Before the change point, the OR (95% CI) was 0.69 (0.58, 0.82). In the analysis of drinking and married status, the interaction was statistically significant. Analysis of mediation showed that alcohol use was responsible for 0.4% (0.10 to 1.2) of the effect of MQItotal on periodontitis. CONCLUSION: In American adults aged over 30, the Muscle Quality Index (MQI) exhibited an independent negative correlation with moderate to severe periodontitis, demonstrating a J-shaped relationship. Furthermore, alcohol consumption may act as a mediator in the association between MQI and periodontitis.

Investigation on the association between serum lipid levels and periodontitis: a bidirectional Mendelian randomization analysis.

OBJECTIVE: Several research has considered the potential correlation between periodontitis and serum lipids. However, serum lipid profiles correlation with periodontitis remains largely unknown. The investigation objective was to examine periodontitis correlation with serum lipid levels using a bidirectional Mendelian randomization (MR) analysis. METHODS: The study employed a bidirectional MR analysis with two samples, utilizing a freely accessible genome-wide association study (GWAS). Furthermore, the primary analysis employed the inverse variance weighted (IVW) method. To determine whether the lipid profiles were associated with periodontitis, a variety of sensitivity analyses (including MR-Egger regression, MR-PRESSO, and weighted median), as well as multivariable MR, were employed. RESULTS: MR analysis performed by IVW did not reveal any relationship between periodontitis and low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides (TG), or total cholesterol (TC). It was also found that LDL, HDL, TG, and TC were not associated to periodontitis. Furthermore, the MR estimations exhibited consistency with other MR sensitivity and multivariate MR (MVMR) analyses. These results show that the correlation between serum lipid levels and periodontitis could not be established. CONCLUSION: The finding indicates a negligible link between periodontitis and serum lipid levels were identified, despite previous observational studies reporting a link between periodontitis and serum lipid levels.

Pyroptosis-related gene signatures are associated with prognosis and tumor microenvironment infiltration in head and neck cancer.

Background and Aims: Recent studies have highlighted the biological significance of pyroptosis in cancer development. Nevertheless, it is still uncertain if pyroptosis also plays a part in immune modulation and the creation of the tumor microenvironment (TME). Methods: The pyroptosis regulatory genes (PRGs) were comprehensively assessed in 1938 head and neck cancer samples, and systematically correlated these modification patterns with the infiltration characteristics of TME cells. The unsupervised consensus analysis method was used to identify specific pyroptosis clusters. The single-sample gene set enrichment analysis and CIBERSOFT algorithms were used to evaluate the infiltration levels of various immune cell subsets. A principal component analysis algorithm was used to construct the pyrolysis potential index (PPI) to quantify the pyrolysis regulation patterns in head and neck squamous cell carcinoma (HNSC). Results: Pyrophosphate regulatory genes (PRGs) are often upregulated in tumors due to mutations. PRGs relate to various clinical outcomes and pathways. Molecular subtyping identified pyroptosis patterns, which align with three tumor immunophenotypes: immune-inflamed, immune-excluded, and immune-desert. The PPI measures pyrolysis roles, showing higher PPI in tumor samples linked to subtypes and clinical characteristics. Lower PPI correlates with longer survival, increased immune activity, more tumor mutations, high PD-L1 expression, and mutations in significant genes like PIK3CA. Such patients also experience enhanced immune responses in immunotherapy trials. Conclusion: We conducted a comprehensive examination of pyroptosis in HNSC and developed a PPI indicator that shows a strong correlation with the variety and intricacy of the TME.

Integrated analysis of NET-DNA receptor CCDC25 in malignant tumors: Pan-cancer analysis.

Background: Previously, it was reported that the coiled-coil domain containing 25 (CCDC25) plays a role in the formation of neutrophil extracellular traps (NETs). This study systematically analyzed the expression profiles of CCDC25 in 30 different types of cancer and one type of blood cancer, acute myeloid leukemia. Methods: The GTEx and CCLE databases were used to evaluate the distribution of CCDC25 expression in both normal tissue and cancer cell lines. A comparison was performed between normal tissue and tumor tissue to analyze the differential expression of CCDC25. We assessed the impact of CCDC25 on the clinical outlook in the TCGA pan-cancer data set by analyzing the Kaplan-Meier survival plot and conducting COX regression analysis. Moreover, the association between the expression levels of CCDC25 and the tumor microenvironment in multiple cancers was conducted. Additionally, the investigation also examined the link between CCDC25 and immune neoantigen, tumor mutational burden, microsatellite instability, mismatch repair genes (MMRs), HLA-related genes, and DNA methyltransferase (DNMT). Results: CCDC25 was expressed in nearly all of the 31 normal tissues while exhibiting a moderate to low level of expression in cancer cell lines. While abnormal expression was detected in the majority of malignancies, there was no link found between elevated CCDC25 levels and overall survival, disease-free survival, recurrence-free survival, and disease-free interval in the TCGA comprehensive cancer data set. Nevertheless, the expression of CCDC25 exhibited a notable link with the infiltration levels of activated CD4 memory T cells, quiescent mast cells, dendritic cells in an activated state, T cells that assist in follicle development, M2 macrophages, and neutrophils in various tumors. Conclusions: In most cancers, the results indicate that there is no link between CCDC25 and prognosis. However, CCDC25 can be targeted for therapeutic purposes concerning metastasis and immune infiltration.

Relationship between periodontitis and COVID-19: A bidirectional two-sample Mendelian randomization study.

Background and Aims: Coronavirus disease (COVID-19) is a major danger to world health and has been linked to periodontitis in a number of epidemiological observational studies. However, it is unclear whether COVID-19 causes periodontitis. COVID-19's causal influence on periodontitis was determined using bidirectional Mendelian randomization (MR). Methods: Large-scale COVID-19 and periodontitis genome wide association study data were analyzed. Inverse variance weighting, MR-Egger, weighted median, and MR-PRESSO were used to estimate causal effects. Sensitivity studies were conducted using the Cochran's Q test, the MR-Egger intercept test, the MR-PRESSO, and the leave-one-out (LOO) analysis. Further investigation of potential mediating factors was performed using risk factor analysis. Results: The MR presented no causal relationship between periodontitis and hospitalization for COVID-19 (odds ratio [OR] = 0.97, 95% confidence interval [CI] 0.78-1.20; p = 0.76), vulnerability to COVID-19 (OR = 1.04, 95% CI 0.88-1.21; p = 0.65), COVID-19 disease severity (OR = 1.01, 95% CI 0.92-1.11; p = 0.81). Meanwhile, a noncausal effect of genetic hospitalization for COVID-19, illness severity, and vulnerability to periodontitis was detected. Other MR methods yielded identical results to inverse variance weighting. According to sensitivity analysis, horizontal pleiotropy is unlikely to affect causal estimation. Conclusion: Periodontitis had no link to the risk of COVID-19 hospitalization, susceptibility, or severity. However, the substance in COVID-19 that is responsible for this effect must be studied further.

Heel bone mineral density and various oral diseases: a bidirectional Mendelian randomization.

INTRODUCTION: Observational studies demonstrated that the relationship between bone mineral density and oral diseases is mixed. To access the association between heel bone mineral density and various oral diseases, we conducted the Mendelian randomization analysis to explore the association. MATERIALS AND METHODS: Two-sample bidirectional Mendelian analysis was used to explore the relationship between heel bone mineral density and various oral diseases. The inverse-variance weighted (IVW) was used as the primary effect estimate, and various methods were applied to test the reliability and stability of the results, namely MR-Egger, weighted median, simple mode, and weighted mode. RESULTS: This study showed that there was a negative relationship between heel BMD and periodontitis when heel BMD was used as an exposure factor and periodontitis as an outcome factor (IVW OR = 0.85; 95% CI, 0.75-0.95; p = 0.005). Bidirectional Mendelian randomization showed that there was no statistically significant association between periodontitis and heel bone mineral density when chronic periodontitis was the exposure factor (p > 0.05). And there was no significant relationship between heel bone mineral density and other oral diseases (dental caries, diseases of pulp and periapical tissues, impacted teeth, cleft lip, and cleft palate, oral and oropharyngeal cancer) (p > 0.05). CONCLUSION: This study showed that there was a negative relationship between heel bone density and periodontitis, and the decrease in heel bone density could promote the occurrence of periodontitis. In addition, there was no statistically significant relationship between heel bone density and other oral diseases.

Association between C-Reactive protein and periodontitis in an obese population from the NHANES 2009-2010.

BACKGROUND: Various data have been obtained on the relationship between body mass index (BMI) and C-reactive protein (CRP) and periodontitis. The aim of this study was to determine whether CRP/BMI are associated with periodontitis using data from the National Health and Nutrition Examination Survey (NHANES) database. METHODS: A cross-sectional analysis of data from 3602 participants in the 2009-2010 NHANES cycle was performed. The definition of periodontitis was used to divide participants into four groups according to the criteria of Eke. Correlations between CRP/BMI and periodontitis were tested for statistical significance by means of descriptive statistics, multivariate regression, and subgroup-stratified analyses, with and without adjustments for confounders (such as age and sex). RESULTS: There were no statistically significant differences (p > 0.05) regarding BMI and the development of periodontitis. After adjustment for age, sex, race, marital status, annual family income, alcohol consumption, hypertension, smoking, chronic pulmonary disease, cardiovascular disease, diabetes, flossing, and arthritis, CRP correlated significantly with the development of periodontitis in the subgroups stratified by obesity, with an odds ratio (OR) of 1.2 (95% CI, 1.0 to 1.5). CONCLUSION: Through data analysis, we found an association between CRP levels and periodontitis prevalence in the American population, although this association was only present in the obese population. While there are several hypotheses about the underlying mechanism, further studies are needed to validate these findings.

Mendelian Randomisation Study on Association of Gut Microbiota and Periodontitis.

OBJECTIVE: Several studies have demonstrated the possible association between gut microbiota and periodontitis. The mechanism by which gut microbiota contribute to periodontitis remains unknown. METHODS: A 2-sample Mendelian randomisation (MR) study was conducted using publicly available Genome-Wide Association Studies (GWAS) data of European ancestry. The relationships between gut microbiota and tooth loss and periodontitis were assessed using summary-level data. Moreover, inverse variance weighted (IVW), MR-Egger, weighted median, and simple Mendelian were used. The results were further validated using sensitivity analyses. RESULTS: A total of 211 gut microbiota were studied, including 9 phyla, 16 classes, 20 orders, 35 families, and 131 genera. The IVW method identified 16 bacterial genera related to the risk of periodontitis and tooth loss. Lactobacillaceae was associated with an increased risk of periodontitis (odds ratio [OR], 1.40, 95% confidence interval [CI], 1.03-1.91, P<.001) and tooth loss (OR, 1.12; 95% CIs, 1.02-1.24, P = .002), whereas Lachnospiraceae UCG008 was linked to a lower risk of tooth loss (P = .041). There was no heterogeneity and horizontal pleiotropy in the sensitivity analysis. CONCLUSIONS: Several microorganisms were identified to be linked to the risk of periodontitis. Furthermore, the findings improved our understanding of gut microbiota and periodontitis pathology.

Integrating GWAS and proteome data to identify novel drug targets for MU.

Mouth ulcers have been associated with numerous loci in genome wide association studies (GWAS). Nonetheless, it remains unclear what mechanisms are involved in the pathogenesis of mouth ulcers at these loci, as well as what the most effective ulcer drugs are. Thus, we aimed to screen hub genes responsible for mouth ulcer pathogenesis. We conducted an imputed/in-silico proteome-wide association study to discover candidate genes that impact the development of mouth ulcers and affect the expression and concentration of associated proteins in the bloodstream. The integrative analysis revealed that 35 genes play a significant role in the development of mouth ulcers, both in terms of their protein and transcriptional levels. Following this analysis, the researchers identified 6 key genes, namely BTN3A3, IL12B, BPI, FAM213A, PLXNB2, and IL22RA2, which were related to the onset of mouth ulcers. By combining with multidimensional data, six genes were found to correlate with mouth ulcer pathogenesis, which can be useful for further biological and therapeutic research.