Association of periodontitis with all-cause and cause-specific mortality among individuals with depression: a population-based study.

To detect the association between periodontitis and all-cause as well as cause-specific mortality rates among adults diagnosed with depression. Participants diagnosed with depression were selected from NHANES across three periods (1988-1994; 1999-2004; 2009-2014). Cox proportional hazards and Weibull accelerated failure time (AFT) models were utilized to calculate hazard ratios (HRs), time ratios (TRs), and their 95% confidence intervals (CIs) to evaluate the association between moderate-to-severe periodontitis and all-cause as well as cause-specific mortality among participants with depression. white blood counts and C-reactive protein were used to assess the mediating role of systemic inflammation. Among the 1,189 participants with a median follow-up of 9.25 years, 133 deaths were recorded. After adjusting for multiple variables, moderate-to-severe periodontitis was obvious associated with an increased risk of cancer-related mortality in individuals with depression (Cox: HR 3.22, 95% CI 1.51-6.83, P = 0.002; AFT: TR 0.70, 95% CI 0.52-0.94, P = 0.017). Neither WBC nor CRP significantly mediate the association between periodontitis and cancer-related mortality. The risk of cancer-related mortality rose with the severity of periodontitis (P for trend = 0.021). However, no association was observed between moderate-to-severe periodontitis and other kinds of mortality. Moderate-to-severe periodontitis is linked to an elevated risk of cancer-related mortality among adults diagnosed with depression, with the mortality risk increasing alongside the severity of periodontitis. No significant mediating effect of systemic inflammation was found in this association. These findings highlight the importance of addressing periodontal health in individuals with depression. By uncovering the association between periodontitis and mortality in this population, our study underscores the potential benefits of preventive dental care and periodontal treatment in reducing the risk of cancer-related mortality in individuals with depression.

Associations of tooth loss with risk of all-cause and cause-specific mortality among US adults with diabetes mellitus.

OBJECTIVES: To determine whether tooth loss affects all-cause and cause-specific mortality in a nationally representative sample of adults with diabetes mellitus (DM) in the United States. METHODS: This prospective cohort study involved 8207 participants aged 30 years or older at baseline, all diagnosed with diabetes mellitus and enrolled in the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018. Tooth loss was stratified into 28 teeth (complete), 20-27 teeth (tooth loss), 9-19 teeth (lacking functional), 1-8 teeth (severe tooth loss) and edentulism. To estimate hazard ratios (HRs) and 95 % confidence intervals (CIs) for all-cause and specific-cause mortality in diabetes mellitus participants according to tooth loss, multivariate cox proportional hazards regression models were used. Relationships between mortality and quartiles of mean tooth loss levels were analyzed, with the lowest quartile as the baseline for comparisons. RESULTS: During a median of 6.92 years of follow-up, 2317 deaths were documented. After multivariate adjustments, higher tooth loss levels were significantly and non-linearly associated with higher risks of all-cause, CVD-related and DM-related mortality among participants with DM. When compared with the reference group of mean tooth loss levels, the highest quartile showed significantly increased risks: all-cause mortality (HR, 2.11; 95 % CI, 1.53-2.91, P-trend < 0.001), CVD-related mortality (HR, 3.24, 95 % CI, 1.54-6.85, P-trend < 0.001) and DM-related mortality (HR, 2.78, 95 % CI, 1.15-6.68, P-trend < 0.001). CONCLUSIONS: Tooth loss is associated with an increased risk of all-cause, CVD-related and diabetes mellitus mortality among adults with diabetes mellitus in the US. CLINICAL SIGNIFICANCE: This study presents evidence for physicians and dentists that higher tooth loss was significantly associated with increased risk of all-cause, CVD-related and diabetes mellitus mortality in a dose-response manner among adults with diabetes mellitus. Therefore, assessment of survival in individuals with diabetes mellitus could pay attention to the tooth loss.

CCR7/DUSP1 signaling Axis mediates iCAF to regulates head and neck squamous cell carcinoma growth.

OBJECTIVE: C-C motif chemokine receptor 7 (CCR7) significantly influences tumors onset and progression, yet its impact on the tumor microenvironment (TME) and specific mechanisms remain elusive. Inflammatory Cancer-Associated Fibroblasts (iCAF), a vital subtype of Cancer-Associated Fibroblasts (CAF), play a critical role in regulating the TME and tumor growth, though the underlying molecular mechanisms are not fully understood. This study aims to determine whether CCR7 participates in tumor regulation by iCAF and to elucidate the specific mechanisms involved. METHODS: Differential gene analysis of CAF subtypes in CCR7 knockout and wild-type groups was conducted using single-cell data. Animal models facilitated the extraction of primary iCAF cells via flow cytometry sorting. Changes in DUSP1 expression and the efficiency of lentivirus-mediated knockdown and overexpression were examined through qPCR and Western Blot. MOC1 and MOC2 cells were co-cultured with iCAF, with subsequent validation of changes in tumor cell proliferation, migration, and invasion using CCK8, EdU, and wound healing assays. ELISA was employed to detect changes in TGF-ß1 concentration in the iCAF supernatant. RESULTS: CAF was categorized into three subtypes-myCAF, iCAF, and apCAF-based on single-cell data. Analysis revealed a significant increase in DUSP1 expression in iCAF from the CCR7 knockout group, confirmed by in vitro experiments. Co-culturing MOC1 and MOC2 cells with iCAF exhibiting lentivirus-mediated DUSP1 knockdown resulted in inhibited tumor cell proliferation, invasion, and migration. In contrast, co-culture with iCAF overexpressing DUSP1 enhanced these capabilities. Additionally, the TGF-ß1 concentration in the supernatant increased in the DUSP1 knockdown iCAF group, whereas it decreased in the DUSP1 overexpression group. CONCLUSION: The CCR7/DUSP1 signaling axis regulates tumor growth by modulating TGF-ß1 secretion in iCAF.

CCR7 affects the tumor microenvironment by regulating the activation of naïve CD8+ T cells to promote the proliferation of oral squamous cell carcinoma.

BACKGROUND: Head and neck cancer is the sixth most common malignancy worldwide, and oral squamous cell carcinoma (OSCC) is the most common head and neck cancer, being one of the leading causes of cancer morbidity and mortality worldwide. CC Chemokine receptor 7(CCR7) is a multifunctional G protein-coupled trans-membrane chemokine that affects immune cell chemotaxis, migration, and cancer progression through its interaction with its ligands C-C motif chemokine ligand 19(CCL19) and C-C motif chemokine ligand 21(CCL21). Numerous studies have demonstrated the involvement of CCR7 in the malignant progression of a variety of cancers, reflecting the pro-cancer properties of CCR7. The Cancer Genome Atlas data suggests CCR7 has elevated expression in oral cancer. Specifically, CCR7 expression in tumor microenvironment (TME) may regulate the ability of some immune cells to engage in anti-tumor immune responses. Since CD8+ T cells have become a key immunotherapeutic target, the role of CCR7 in antitumor immune response of naïve CD8+ T cells in TME has not been thoroughly investigated. METHODS: A CCR7 knockout mouse model was constructed, and the mechanism of ccr7 on the regulation of tumor microenvironment by naïve CD8+ T cells was verified under the guidance of single-cell RNA sequencing combined with in vivo animal experiments and in vitro cell experiments. RESULTS: CCR7 is knocked out with impaired tumor growth and altered CD8+ T cell profiles, revealing the importance of this protein in OSCC. CONCLUSIONS: Inhibition of CCR7 enhances CD8+ T cell activation, proliferation, and anti-tumor function, suggesting its potential as a therapeutic target.

Analysis of the effect of CCR7 on the microenvironment of mouse oral squamous cell carcinoma by single-cell RNA sequencing technology.

BACKGROUND: Studies have shown that CCR7, an important inflammatory factor, can promote the proliferation and metastasis of oral squamous cell carcinoma (OSCC), but its role in the tumor microenvironment (TME) remains unclear. This paper explores the role of CCR7 in the TME of OSCC. METHODS: In this work, we constructed CCR7 gene knockout mice and OSCC mouse models. Single-cell RNA sequencing (scRNA-seq) and bioinformatics were used to analyze the differences in the OSCC microenvironment between three CCR7 gene knockout mice (KO) and three wild-type mice (WT). Immunohistochemistry, immunofluorescence staining, and flow cytometry were used to analyze the expression of key genes in significantly different cell types between the KO and WT groups. An in vitro experiment was used to verify the effect of CCR7 on M2 macrophage polarization. RESULTS: In the mouse OSCC models, the tumor growth rate in the KO group was significantly lower than that in the WT group. Eight main cell types (including tumor cells, fibroblasts, macrophages, granulocytes, T cells, endothelial cells, monocytes, and B cells) were identified by Seurat analysis. The scRNA-seq results showed that the proportion of tumor cells was lower, but the proportion of inflammatory cells was significantly higher in the KO group than in the WT group. CellPhoneDB analysis results indicated a strong interaction relationship between tumor cells and macrophages, T cells, fibroblasts, and endothelial cells. Functional enrichment results indicated that the expression level of the Dusp1 gene in the KO group was generally higher than that in the WT group in various cell types. Macrophage subclustering results indicated that the proportion of M2 macrophages in the KO group was lower than that in the WT group. In vitro experimental results showed that CCR7 can promote M2 macrophage polarization, thus promoting the proliferation, invasion and migration of OSCC cells. CONCLUSIONS: CCR7 gene knockout can significantly inhibit the growth of mouse oral squamous cell carcinoma by promoting the polarization of M2 macrophages.

Associations of periodontitis with risk of all-cause and cause-specific mortality among us adults with chronic kidney disease.

OBJECTIVES: To investigate the associations of periodontitis with risk of all-cause and cause-specific mortality in a nationally representative sample of adults with chronic kidney disease (CKD) in the United States. METHODS: This prospective cohort study included 4,271 individuals aged ≥30 years at baseline with CKD participants in the National Health and Nutrition Examination Survey (NHANES) during 1988-1994, 1999-2004, and 2009-2014. CKD was defined as an estimated glomerular filtration rate (eGFR) <60 ml/min/1.73m2 and/or urinary albumin/creatinine ratio (uACR) ≥30 mg/g. Multivariate cox proportional hazards regression models were used to estimate the hazard ratios (HRs) and 95 % confidence intervals (CIs) of all-cause and cause-specific mortality in participants with CKD according to periodontitis. The associations of the quartiles of mean clinical attachment loss (CAL) and mean periodontal probing depth (PPD) levels with mortality were examined using the first quartile as the reference group. RESULTS: During a median of 8.67 years of follow-up, 2,146 deaths were documented. After multivariate adjustments, moderate/severe periodontitis was significantly associated with all-cause (HR:1.28; 95 % CI:1.11-1.47; P = 0.001) and cardiovascular disease (CVD)-related mortality (HR:1.44; 95 % CI:1.14-1.81; P = 0.002) in participants with CKD. Compared with the reference group of mean CAL and mean PPD levels, all-cause (CAL: HR, 1.58; 95 % CI, 1.32-1.89, P <0.001; PPD: HR, 1.35, 95 % CI, 1.09-1.67, P = 0.011) and CVD-related mortality (CAL: HR, 1.70, 95 % CI, 1.21-2.40, P = 0.001) were increased for participants in the highest quartile. CONCLUSIONS: This study suggests that moderate/severe periodontitis and high levels of mean CAL and mean PPD are associated with an increased risk of all-cause mortality, and moderate/severe periodontitis and mean CAL associated with CVD-related mortality among adults with CKD in the US. CLINICAL SIGNIFICANCE: This study details the association between periodontitis and the increased risk of all-cause mortality and CVD-related mortality in a large, representative sample of adults with CKD.

Improving masticatory and swallowing ability of postoperative oral and maxillofacial tumor patients by telerehabilitation-A randomized controlled trial.

OBJECTIVE: To evaluate the effect of telerehabilitation on oral function of oral and maxillofacial tumor patients. DESIGN: Unicentral, single-blind, randomized controlled trial. SETTING: Community. SUBJECTS: Patients with primary oral and maxillofacial tumor receiving surgical treatment. INTERVENTIONS: Telerehabilitation guidance from therapists. MAIN MEASURES: At the beginning of training (T0) and 1 month (T1), 3 months (T2) and 6 months (T3) after training, patients' masticatory ability (mastication efficiency-masticatory performance evaluating gum, maximum bite force and mouth opening) and swallowing ability (water swallowing test) was measured. Modified Sato questionnaire and MD Anderson dysphagia inventory (MDADI) were used for self-evaluation of masticatory and swallowing ability. RESULTS: A total of 64 participants (intervention: 33; control: 31) were included. The masticatory efficiency scores of the intervention group were significantly better than those of the control group at T2 (intervention: 3.67 (0.48); control: 3.03 (0.85)) and T3 (intervention: 4.20 (0.30); control: 3.50 (0.79)); and maximum mouth opening was better at T2 (intervention: 3.18 (0.59); control: 2.77 (0.54)) and T3 (intervention: 3.54 (0.58); control: 3.09 (0.41)). In water swallowing test, the intervention group had better scores at T2 and T3. The scores of MDADI scale in intervention group were better than those in the control group after 3 months of training. In subgroup analysis, the intervention group of oral cancer patients had better swallowing function at T2 and T3, but no significant difference was found in the subgroup of oropharyngeal cancer. CONCLUSIONS: Telerehabilitation could greatly improve the long-term (3-6 months) training effect under the condition of greatly saving medical resources and reducing personnel contact.

The role of p21-activated kinase 4 in the progression of oral squamous cell carcinoma by targeting PI3K-AKT signaling pathway.

BACKGROUND: Oral squamous carcinoma (OSCC), the most common head and neck malignancy, has a strong propensity for malignant proliferation and metastasis, which will decrease the survival of patients. P21-activated kinase 4 (PAK4), a classical serine/threonine protein kinase with multiple cellular functions, has an essential role in cancer cell migration and invasion. Here, we elucidated the function and possible molecular mechanisms of the effect of PAK4 on the biological behaviors of OSCC. METHODS: The expression of genes and protein was detected by real-time PCR and western blotting. We used oral squamous carcinoma cell lines, Tca8117, Cal 27, SCC 4, and SCC 9 for validation of our cell function data. Flow cytometry, 3D cultures, and clone formation assay were used to detect proliferation of cells. RNA sequencing and bioinformatic analysis was performed to determine the potential function of PAK4. RESULTS: Immunohistochemistry, western blotting and real-time PCR demonstrated that PAK4 expression was up-regulated in OSCC tissues. Overexpression of PAK4 promoted the proliferation, migration and invasion of OSCC cell lines. RNA sequencing (RNA-seq) for the transcriptome-wide analysis of differential gene expression followed by bioinformatic analysis was performed to determine the potential function of PAK4. Based on the KEGG enrichment analysis and GO analysis of differential expression genes (DEGs) we found that PAK4 promotes the cell-cycle machinery, which associated with 44 regulated genes, thereby promoting cancer cell differentiation. CONCLUSIONS: This study demonstrates that the PAK4 regulates the biological behaviors of OSCC by PI3K-AKT signaling pathway, and these findings might provide a novel strategy for OSCC treatment.

Is periodontal disease a risk indicator for urogenital cancer? A systematic review and meta-analysis of cohort studies.

Objectives: The objective of the present work was to conduct a systematic review and meta-analysis to assess the association between periodontal disease (PD) and urogenital cancer (UC) risk. Materials and methods: An electronic search in PubMed, EMBASE, the Cochrane Library, and Web of Science was conducted using MeSH terms to identify cohort studies published before May 17, 2022. Cohort studies examining the association between PD and UC risk were included. We used a random-effects model to summarize the effect sizes with 95% confidence intervals (CIs) of the included studies with PD as the indicator and UC as the outcome. Results: Eleven cohort studies met the inclusion criteria. Our results suggest that PD patients increases the risk of UC by 1.24-fold (hazard ratio (HR), 1.24; 95% CI, 1.17-1.31; I2, 22.4%). The strength of the sensitivity analysis and cumulative meta-analysis confirmed the reliability of the results. Conclusion: We found that PD is a potential risk factor for UC. Our results indicate that along with the decrease in the incidence of PD,PD treatment may help prevent UC. We hope that our study will raise awareness of periodontal health, thereby reducing the incidence of UC. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42021244405.

CC chemokine receptor 7 promotes macrophage recruitment and induces M2-polarization through CC chemokine ligand 19&21 in oral squamous cell carcinoma.

PURPOSE: This study aimed to investigate the impact of CC chemokine receptor 7 (CCR7) on the recruitment and polarization of tumor-associated macrophages (TAMs) in oral squamous cell carcinoma (OSCC). METHODS: We analyzed CCR7 expression pattern, clinicopathological significance, and its association with M2 macrophage infiltration in OSCC by bioinformatic methods. Small interfering RNA (siRNA) was utilized to silence CCR7 in OSCC cells. Conditioned media (CM) was harvested from transfected OSCC cells to establish a co-culture model of THP-1 derived macrophages and OSCC cells. Transwell assay and cell adhesion assay were performed to examine the effect of CCR7 on macrophages recruitment and adhesion. Cytoskeleton was labelled by phalloidin to observe macrophage morphological changes. Moreover, phenotypic alteration of macrophages was measured using quantitative real-time PCR (qRT-PCR), flow cytometry, and immunofluorescence (IF) staining. Ultimately, recombinant human CCL19 and CCL21 were added into the medium of THP-1 derived macrophages to explore their effects on polarization in vitro. RESULTS: In OSCC patients, the overexpression of CCR7 positively correlated with lymph node metastasis and M2 macrophage infiltration. Macrophage not only exhibited enhanced migration, invasion and adhesion abilities, but also appeared more spindle and branched in vitro when treated with CM from OSCC cells. However, these phenomena were abrogated with knockdown of CCR7. We also discovered that inhibition of CCR7 in OSCC cells suppressed TAMs polarization to an M2 phenotype. In addition, recombinant human CCL19 and CCL21 promoted macrophage M2-polarization in vitro. CONCLUSION: CCR7 in OSCC cells promoted recruitment and M2-polarization of THP-1 derived macrophages in vitro by regulating production of CCL19 and CCL21.