U-shaped association between pan-immune-inflammation value and periodontitis: NHANES 2009-2014.

BACKGROUND: This study aimed to investigate the relationship between the pan-immune-inflammation value (PIV) and periodontitis based on a large national survey. METHODS: In the present cross-sectional study, data were obtained from the National Health and Nutrition Examination Survey (NHANES) 2009-2014, which included a total of 10,300 participants. The categorization of periodontitis was based on the 2017 classification scheme. The PIV was determined using the formula: (neutrophils count × monocyte count × platelet count)/lymphocytes count. Restricted cubic spline and weighted multivariable logistic regression analyses were employed to evaluate the associations between the PIV with periodontitis. RESULTS: The associations between PIV and stage III/IV periodontitis followed a U-shaped pattern (Pnon-linearity < 0.001). The risk of developing stage III/IV periodontitis showed an increasing trend among participants in the first quartile (odds ratio [OR] = 1.21; 95% confidence interval [CI]: 1.01-1.46), third quartile (OR = 1.34; 95% CI: 1.11-1.61), and fourth quartile (OR = 1.47; 95% CI: 1.25-1.73) compared to those in the second quartile. Subgroup analysis indicated stronger associations of PIV with periodontitis in males (ORQ4vs2 = 1.72, 95% CI: 1.36-2.18) and individuals with hypertension (ORQ4vs2 = 1.78, 95% CI: 1.38-2.28) with significant interactions (Pinteraction < 0.05). CONCLUSIONS: There is a U-shaped association between PIV and stage III/IV periodontitis, which suggests a potential adjunctive treatment strategy for periodontitis. Higher PIV values were found to have a stronger correlation with stage III/IV periodontitis in males and individuals with hypertension. Further prospective trials are needed to confirm the validity of our results. PLAIN LANGUAGE SUMMARY: A U-shaped association exists between the pan-immune inflammation value and periodontitis in US adults, suggesting that maintaining a moderate immune inflammation response is crucial for periodontal health.

Association between relative fat mass and periodontitis: results from NHANES 2009-2014.

Relative fat mass (RFM) is a novel indicator for measuring body fat. This cross-section study aims to explore the association between RFM and periodontitis and to investigate possible effect modifiers in U.S. adults based on the National Health and Nutrition Examination Survey 2009-2014. The category of periodontitis was defined by the CDC/AAP. Mean clinical attachment loss and mean pocket probing depth (PPD) were calculated. The RFM formula is: 64 - (20 × height/WC) + (12 × sex), with sex coded as 1 for female and 0 for male. Natural cubic spline and weighted multivariable regression analyses were conducted to investigate the relationship between RFM and periodontal status. Subgroup and interaction analyses were also employed to assess the moderating roles of age, gender, and race. A total of 10,307 participants were included in our study. Compared to the lowest quartiles, individuals in the highest quartiles of RFM levels were more likely to have moderate/severe periodontitis (ORQ4vs1 = 1.64, 95% CI 1.30-2.06) and had a higher mean PPD (ßQ4vs1 = 0.15, 95% CI 0.09-0.22). This association was particularly stronger in populations under the age of 60, with significant interactions. Taken together, RFM is positively associated with periodontitis, particularly in those under 60 years old.

Causal Relationship between Mitochondrial Biological Function and Periodontitis: Evidence from a Mendelian Randomization Study.

A growing number of studies indicate that mitochondrial dysfunction serves as a pathological mechanism for periodontitis. Therefore, this two-sample Mendelian randomization (MR) study was carried out to explore the causal associations between mitochondrial biological function and periodontitis, because the specific nature of this causal relationship remains inconclusive in existing MR studies. Inverse variance weighting, Mendelian randomization-Egger, weighted mode, simple mode, and weighted median analyses were performed to assess the causal relationships between the exposure factors and periodontitis. The results of the present study revealed a causal association between periodontitis and medium-chain specific acyl-CoA dehydrogenase (MCAD), malonyl-CoA decarboxylase (MLYCD), glutaredoxin 2 (Grx2), oligoribonuclease (ORN), and pyruvate carboxylase (PC). Notably, MCAD and MLYCD are causally linked to periodontitis, and serve as protective factors. However, Grx2, ORN, and PC function as risk factors for periodontitis. Our study established a causal relationship between mitochondrial biological function and periodontitis, and such insights may provide a promising approach for treating periodontitis via mitochondrial regulation.

Associations of dietary antioxidant intake with periodontal health among US adults: An exploratory mediation analysis via mitochondrial function.

AIM: To assess the relationship between dietary antioxidant intake and periodontal health in US adults and the potential role of mitochondrial function. MATERIALS AND METHODS: We performed a cross-sectional study using data from the National Health and Nutrition Examination Survey (NHANES) 2011-2014. Dietary antioxidant intake was evaluated using three diet-related indices: dietary oxidative balance score (DOBS), dietary total antioxidant capacity (DTAC) of antioxidant vitamins and composite dietary antioxidant index (CDAI). Periodontal parameters included attachment loss (AL) and probing pocket depth (PPD). Mitochondrial dysfunction was assessed using the methylmalonic acid (MMA) level. Weighted multivariable linear regression analyses were employed to investigate the association between dietary antioxidant intake and periodontal status. Additionally, exploratory mediation analyses were conducted to determine the mediating effect of MMA on the association. RESULTS: Totally, 5520 participants were included in our study. Participants with higher DOBS and DTAC scores had lower mean AL/PPD and MMA values. CDAI was negatively associated with mean AL and PPD. Furthermore, MMA mediated 9.4% and 4.9% of the associations between DOBS and mean AL and mean PPD, respectively. MMA also accounted for 7.2% and 3.3% of the association between DTAC and mean AL and PPD, respectively. CONCLUSIONS: The findings support that dietary antioxidant intake helps in improving periodontal health, possibly and partially by enhancing mitochondrial function.

Persistent infection with Porphyromonas gingivalis increases the tumorigenic potential of human immortalised oral epithelial cells through ZFP36 inhibition.

The association between Porphyromonas gingivalis infection and oral squamous cell carcinoma (OSCC) has been established by numerous epidemiological studies. However, the underlying mechanism specific to this connection remains unclear. By bioinformatical analysis, we identified ZFP36 as a potentially significant co-expressed gene in both the OSCC gene database and the persistent infection model of P. gingivalis. To further investigate the role of ZFP36, we established a cell model that human immortalized oral epithelial cells (HIOECs) that were sustainedly infected by P. gingivalis (MOI = 1) for a duration of 30 weeks. Our findings indicated that sustained infection with P. gingivalis inhibited the expression of ZFP36 protein and induced changes in the biological behaviour of HIOECs. The mechanism investigation demonstrated the potential role of ZFP36 in regulating the cancer-related biological behaviour of HIOECs. Subsequent studies revealed that highly expressed CCAT1 could serve as a molecular scaffold in the formation of the ZFP36/CCAT1/MK2 complex. This complex formation enhanced the binding abundance of MK2 and ZFP36, thereby promoting the inhibition of ZFP36 protein phosphorylation. To summarize, low expression of ZFP36 protein under persistent P. gingivalis infection enhances the cancer-related biological behaviour of HIOECs.

Association between ethylene oxide exposure and periodontitis: a cross-sectional study from NHANES 2013-2014.

BACKGROUND: Exposure to ethylene oxide (EO) induces inflammation and oxidative stress, which are the main mechanisms of periodontitis. However, the effect of EO on periodontal health is not unclear. In this study, we aimed to explore the relationship between EO exposure and the risk of periodontitis in general US adults. METHODS: Data used in our study from the National Health and Nutritional Examination Survey (NHANES) 2013-2014. The EO biomarker, hemoglobin adduct of EO (HbEO), was measured in blood samples utilizing high-performance liquid chromatography-tandem mass spectrometry. Periodontitis category was defined by the CDC/AAP according to clinical periodontal parameters. Natural cubic spline, weight multivariable logistic regression analyses and subgroup analysis were used to explore the association between EO exposure and the risk of periodontitis. RESULTS: A total of 1497 participants over the age of 30 were included in our study. A non-linear positive association with periodontitis was identified for HbEO levels. Participants in the highest tertile of HbEO levels were more likely to have poorer periodontal health compared to the lowest tertile (ORtertile3vs1 = 2.80, 95% CI: 1.85-4.24). Similar results were also found in different subgroups. CONCLUSIONS: HbEO levels are positively associated with poor periodontal health in US adults. Additional longitudinal studies are necessary to further enhance our comprehension of the impact of exposure to EO on periodontal status.

J-shaped association between systemic immune-inflammation index and periodontitis: Results from NHANES 2009-2014.

BACKGROUND: To examine the relationship between the systemic immune-inflammation index (SII) and periodontitis and to investigate possible effect modifiers. METHODS: Data used in the present cross-sectional study are from the National Health and Nutrition Examination Survey (NHANES) 2009-2014 (N = 10,301). The SII was calculated using the following formula: (neutrophils count × platelet count)/lymphocytes count. The category of periodontitis was defined by the Centers for Disease Control and Prevention and American Academy of Periodontology (CDC/AAP) classification. We employed natural cubic spline and multivariable logistic regression analyses to evaluate the associations of the SII with periodontitis. RESULTS: The associations between SII and periodontal health followed a J-shape (p < 0.001). The risk of periodontitis tended to reduce with the increment of log2 (SII) in participants with log2 (SII) ≤ 8.66 (odds radio [OR] = 0.83; 95% CI: 0.69-0.999), especially among non-Hispanic Whites (OR = 0.70; 95% CI: 0.52-0.95), and increased with the increment of log2 (SII) in participants with log2 (SII) > 8.66 (OR = 1.19; 95% CI: 1.02-1.38). A similar trend was also observed between the SII and the number of sites with probing pocket depth (PPD) ≥4 mm and clinical attachment loss (CAL) ≥ 3 or 5 mm. Furthermore, we found a significantly stronger correlation between lymphocytes and either neutrophils or platelets in individuals with log2 (SII) > 8.66, as opposed to those with log2 (SII) ≤ 8.66. CONCLUSIONS: There is a J-shaped association between SII and periodontitis in US adults, with an inflection point of log2 (SII) at 8.66, which may provide potential adjunctive treatment strategies for periodontitis with different immune response states. Further prospective trials are still required to confirm our findings.

Association between serum HE4 and poor periodontal health in adult women.

OBJECTIVES: The aim of this study is to explore the association between serum human epididymal protein (HE4) levels and poor periodontal health. MATERIALS AND METHODS: Data used in our study from the National Health and Nutrition Examination Survey (NHANES) 2001-2002 and Gene Expression Omnibus database (GSE10334 and GSE16134). Periodontitis category was defined by the 2017 classification scheme based on clinical periodontal parameters. Univariate and multivariate logistic regression analyses were used to explore the relationship between serum HE4 levels and the risk of periodontitis. GSEA analysis was performed to investigate the function of HE4. RESULTS: A total of 1715 adult women over the age of 30 were included in our study. Compared with the lowest tertile, individuals in the highest tertile of HE4 levels were more likely to be Stage III/IV periodontitis (ORtertile3vs1 = 2.35, 95% CI: 1.35-4.21). The association was still significant in populations who were less than 60 years old, non-Hispanic white, high school graduate, 1.3 < PI ≤ 3.5, non-smoker, current smoker, non-obese, obese, and who had not diabetes mellitus or had not hypertension. In addition, HE4 expression was upregulated in diseased gingival tissues and involved in cell proliferation and immunity. CONCLUSIONS: Serum HE4 is positively associated with poor periodontal health in adult women. CLINICAL RELEVANCE: Patients with high serum HE4 levels are more likely to have Stage III/IV periodontitis. HE4 has the potential to be used as a biomarker to predict the severity of periodontitis.

Association between retinol intake and periodontal health in US adults.

BACKGROUND: Inflammation and oxidative stress are two hallmarks of periodontitis. Retinol is an antioxidant and suppresses expression of pro-inflammatory factors. However, the evidence for an association between retinol intake and periodontitis is limited. Thus, the aim of this study is to assess the association between retinol intake and periodontal health. METHODS: Data used in this cross-sectional study from the National Health and Nutrition Examination Survey (NHANES) 2009-2014 (n = 9081). Dietary intake of retinol was measured based on two 24-h dietary recall interviews. The category of periodontitis was defined by the CDC/AAP according to clinical periodontal parameters. Univariate and multivariate logistic regression analyses were applied to investigate the relationship between retinol intake and the risk of periodontitis. RESULTS: Compared with the lowest tertile, individuals in the highest tertile of retinol intake were less likely to be periodontitis (ORtertile3vs1 = 0.79, 95% CI: 0.65-0.96). The association was still significant in populations who were less than 60 years old (ORtertile3vs1 = 0.80, 95% CI: 0.65-0.97), non-Hispanic black (ORtertile3vs1 = 0.62, 95% CI: 0.42-0.94), PI ≤ 1.3 (ORtertile3vs1 = 0.72, 95% CI: 0.55-0.93), 1.3 < PI ≤ 3.5 (ORtertile3vs1 = 0.70, 95% CI: 0.55-0.89), non-smoker (ORtertile3vs1 = 0.63, 95% CI: 0.48-0.81), obesity (ORtertile3vs1 = 0.68, 95% CI: 0.49-0.94) and who had not diabetes mellitus (ORtertile3vs1 = 0.79, 95% CI: 0.65-0.95) or had hypertension (ORtertile3vs1 = 0.63, 95% CI: 0.47-0.84). CONCLUSION: Retinol intake is inversely associated with poor periodontal health in US adults.

SESN1, negatively regulated by miR-377-3p, suppresses invasive growth of head and neck squamous cell carcinoma by interaction with SMAD3.

Sestrin 1 (SESN1) is a stress-inducible protein that suppresses tumors in numerous cancers. However, the function of SESN1 in head and neck squamous cell carcinoma (HNSCC) is not clear and needs to be elucidated. Here, SESN1 expression was downregulated in HNSCC tissues and cell lines, and low SESN1 expression was positively correlated with poor prognosis in patients with HNSCC. Moreover, SESN1 overexpression inhibited the proliferation, migration, and invasion of HSC-6 and CAL-33 cells. In addition, the binding relationship between miR-377-3p and SESN1 was confirmed using luciferase reporter and RNA immunoprecipitation assays. Downregulation of SESN1 expression was consistent with high levels of miR-377-3p in HNSCC tissues. Linear regression analysis of clinical HNSCC tissues revealed a negative correlation between miR-377-3p and SESN1 expression. Moreover, co-immunoprecipitation mass spectrometry analysis revealed that SESN1 interacted with SMAD3, and SMAD3 reversed the increased proliferation, migration, and invasion of HSC-6 and CAL-33 cells caused by SESN1 knockdown. In conclusion, these findings provide evidence that SESN1 functions as a tumor suppressor and reveal the miR-377-3p-SESN1-SMAD3 regulatory axis that contributes to proliferation, migration, and invasion in HNSCC development, which may represent an interventional target for HNSCC therapy.