Periodontal conditions of teeth adjacent to dental implants with or without peri-implantitis after non-surgical therapy in patients treated for periodontitis: A retrospective study.

OBJECTIVES: To retrospectively assess the periodontal conditions of teeth adjacent to and contralateral to implants presenting with or without peri-implantitis, following non-surgical periodontal and peri-implant mechanical therapy. MATERIALS AND METHODS: One hundred and one patients with existing dental implants and chronic periodontitis, who underwent non-surgical periodontal and peri-implant mechanical therapy, were included. The periodontal clinical probing depth (PPD), gingival recession (GR), and bleeding on probing (BOP) were recorded at six sites around the adjacent (Adj-) teeth and the contralateral (CL-) teeth relative to the implant. The potential factors influencing the periodontal conditions of 316 teeth were analyzed by multivariate linear regression models with generalized estimating equation methods and α = .05. RESULTS: The PPD of Adj-teeth was significantly different from that of CL-teeth before and after non-surgical therapy when the implant was diagnosed with peri-implantitis (PI) (p < .05). The PPD of teeth was shown to be affected by neighboring implants diagnosed with peri-implantitis (ß = .825 mm, p < .001), teeth adjacent to implants (ß = .245 mm, p = .004), a molar tooth type (ß = .435 mm, p = .019), and non-surgical therapy (ß = -.522 mm, p < .001). CONCLUSIONS: Relatively compromised periodontal conditions at Adj-teeth after non-surgical PI therapy were detected. Therefore, clinicians should be aware that non-surgical therapy may be less successful at teeth adjacent to implants with PI.

A bispecific antibody AP203 targeting PD-L1 and CD137 exerts potent antitumor activity without toxicity.

BACKGROUND: Bispecific antibody has garnered considerable attention in the recent years due to its impressive preliminary efficacy in hematological malignancies. For solid tumors, however, the main hindrance is the suppressive tumor microenvironment, which effectively impedes the activation of infiltrating T cells. Herein, we designed a bispecific antibody AP203 with high binding affinity to PD-L1 and CD137 and assessed its safety and anti-tumor efficacy, as well as explored the mechanism of action. METHODS: The optimal antibody binders against PD-L1 and CD137 were screened from the OmniMab phagemid library. The binding affinity of the constructed AP203 were evaluated using enzyme-linked immunosorbent assay (ELISA) and biolayer interferometry (BLI). T-cell stimulatory capacity was assessed using the allogeneic mixed lymphocyte reaction (MLR), antigen-specific recall response, and coculture with PD-L1-expressing cells. In vivo antitumor efficacy was evaluated using two models of tumor-xenografted humanized mice with profiling of tumor infiltrating lymphocytes (TILs). The possible toxicity of AP203 was examined using in vitro cytokine release assay by human PBMCs. RESULTS: AP203, which simultaneously targeted PD-L1 and costimulatory CD137, elicit superior agonistic effects over parental antibodies alone or in combination in terms of T cell activation, enhanced memory recall responses, and overcoming Treg-mediated immunosuppression (P < 0.05). The agonistic activity of AP203 was further demonstrated PD-L1-dependent by coculturing T cells with PD-L1-expressing cells. In vivo animal studies using immunodeficient or immunocompetent mice both showed a dose-related antitumor efficacy superior to parental antibodies in combination (P < 0.05). Correspondingly, AP203 significantly increased tumor infiltrating CD8 + T cells, while decreased CD4 + T cells, as well as Treg cells (P < 0.05), resulting in a dose-dependent increase in the CD8 + /CD4 + ratio. Moreover, either soluble or immobilized AP203 did not induce the production of inflammatory cytokines by human PBMCs. CONCLUSIONS: AP203 exerts potent antitumor activity not only by blocking PD-1/PD-L1 inhibitory signaling, but also by activating CD137 costimulatory signaling in effector T cells that consequently counteracts Treg-mediated immunosuppression. Based on promising preclinical results, AP203 should be a suitable candidate for clinical treatment of solid tumors.

Complement components C3b and C4b as potential reliable site-specific diagnostic biomarkers for periodontitis.

OBJECTIVE: This study aimed to investigate the correlation between the expression levels of C3b and C4b in human gingival tissue (GT) and gingival crevicular fluid (GCF) and disease severity in human periodontitis and to determine whether C3b and C4b are significant site-specific complementary diagnostic markers for periodontitis. BACKGROUND: A variety of biomarkers that have potential for informing diagnoses of periodontitis have been proposed. The complement components C3b and C4b were found to be positively correlated with disease severity. The therapeutic effect of targeting C3b and C4b on inflammatory bone loss in experimental periodontitis models has been studied. However, studies on the diagnostic potential of the gingival C3b and C4b expression levels for periodontitis are scarce. METHODS: The expression levels of C3b and C4b in the GT and GCF were investigated via immunohistochemistry and enzyme-linked immunosorbent assay, respectively. The correlation between the expression levels of C3b and C4b and disease severity with probing depth as well as the clinical attachment level were determined. To evaluate the diagnostic accuracy of the C3b and C4b expression levels at the periodontitis sites, the receiver operating characteristic (ROC) curve, cut-off point, area under the ROC curve, sensitivity, and specificity were analyzed. RESULTS: The expression levels of C3b and C4b in human GT and GCF were significantly positively correlated with periodontitis severity. The expression levels of combined C3b + C4b in the GT can significantly differentiate the disease status at the tissue level (p < .0001). Similarly, the expression levels of C3b + C4b in GCF can statistically distinguish periodontitis sites from healthy ones (p < .0001). CONCLUSIONS: Locally deposited C3b and C4b were positively correlated with periodontitis severity and recognized as site-specific diagnostic biomarkers for clinicopathological features in periodontitis. The association between the C3b and C4b network and periodontitis may be further understood and provide a basis for the development of novel screening as well as diagnostic and therapeutic strategies for periodontitis.

Targeting therapeutic agent against C3b/C4b, SB002, on the inflammation-induced bone loss in experimental periodontitis.

AIMS: To use experimental periodontitis models in rats to investigate the correlation between local expression of the complement components C3b and C4b in periodontal tissues and disease severity, and to assess the therapeutic effects of targeting C3b/C4b on inflammatory bone loss. MATERIALS AND METHODS: The gingival expression of C3, C3b, and C4b in animal experimental periodontitis models were analysed immunohistochemically. The therapeutic effects of the C3b/C4b inhibitor (SB002) on ligation-induced experimental periodontitis was examined using biochemical, histological, and immunohistochemical analyses. RESULTS: The gingival expression levels of C3, C3b, and C4b were positively correlated with the severity of periodontitis. Moreover, both single and multiple injections of the C3b/C4b inhibitor had preventive and therapeutic effects on alveolar bone loss in ligation-induced experimental periodontitis with no associated adverse consequences. CONCLUSIONS: The association between C3b/C4b and periodontitis may provide a basis for the development of novel therapeutic strategies for periodontitis and other inflammatory diseases.

Chlorhexidine gel topical application ameliorates inflammatory bone loss in experimental periodontitis.

OBJECTIVES: This study aimed to evaluate the impact of chlorhexidine (CHX) gel on inflammation-induced periodontal tissue destruction, osteoclastogenesis, subgingival microbiota, and on the modulation of the RANKL/OPG as well as inflammatory mediators during bone remodeling in vivo. MATERIALS AND METHODS: Ligation- and LPS injection-induced experimental periodontitis were created to investigate the effect of topical application of CHX gel in vivo. Alveolar bone loss, osteoclast number and gingival inflammation was evaluated by micro-CT, histological, immunohistochemistry and biochemical analysis. The composition of the subgingival microbiota was characterized by 16S rRNA gene sequencing. RESULTS: Data shows significant decreases in the alveolar bone destruction in rats from ligation-plus-CHX gel group compared to ligation group. In addition, significant decreases in the number of osteoclasts on bone surface and the protein level of receptor activator of nuclear factor κB ligand (RANKL) in gingival tissue were observed in rats from ligation-plus-CHX gel group. Moreover, data shows significantly decreased inflammatory cell infiltration and decreased expression of cyclooxygenase (COX-2) and inducible NO synthase (iNOS) in gingival tissue from ligation-plus-CHX gel group versus ligation group. Assessment of the subgingival microbiota revealed changes in rats with CHX gel application treatment. CONCLUSION: HX gel presents protective effect on gingival tissue inflammation, osteoclastogenesis, RANKL/OPG expression, inflammatory mediators, and alveolar bone loss in vivo, which may have a translational impact on the adjunctive use in the management of inflammation-induced alveolar bone loss.

The referral pattern and treatment modality for peri-implant disease between periodontists and non-periodontist dentists.

OBJECTIVES: This study is to investigate the referral pattern and treatment modality of dentists in the management of peri-implant diseases between periodontists and non-periodontist dentists (NPDs). MATERIALS AND METHODS: A total of 167 validated questionnaires were obtained from periodontists and NPDs, who had experience of placing implants for at least one year. Question I to IV asked how the dentist would respond if a patient came for treatment of their peri-implant diseases with four different scenarios according to resource of patient and disease severity. For each Scenario, dentists also replied which treatment procedures they would use if they decide to treat the patient. RESULTS: Periodontal training, resource of patient, and disease severity were shown to significantly influence the referral pattern and treatment modality in the management of peri-implant disease (p < 0.05). Periodontists were more likely to use variable treatment procedures, including occlusal adjustment (OR = 2.283, p < 0.01), oral hygiene instruction (OR = 3.751, p < 0.001), topical antiseptic agent (OR = 2.491, p < 0.005), non-surgical mechanical therapy (OR = 2.689, p < 0.001), surgical therapy (OR = 2.009, p < 0.01), and remove implant (OR = 3.486, p < 0.001) to treat peri-implant diseases, compared to NPDs. CONCLUSION: The periodontal specialty training, resource of patient, and disease severity significantly influenced the referral pattern and treatment modality of dentist treating an implant diagnosed with peri-implant disease. This study also highlighted the importance of educating basic periodontal and peri-implant disease-related knowledge to all dentists regularly performing dental implant treatments. CLINICAL RELEVANCE: Peri-implant diseases are highly prevalent among patients with dental implants. Periodontal specialty training could enhance using variable treatment procedures to treat peri-implant diseases for dentists.

Periodontitis, Helicobacter pylori infection, and gastrointestinal tract cancer mortality.

AIM: Periodontitis has been proposed to lead to Helicobacter pylori infection, which could cause many gastrointestinal tract cancers. This study aimed to determine the association or otherwise between periodontitis and survival outcomes in individuals with respect to H. pylori infection. MATERIALS AND METHODS: The study population comprised 4955 subjects aged 20-90 who had received both periodontal examination and H. pylori serum test in the Third National Health and Nutrition Examination Survey (NHANES III) database. Logistic regression models were used to analyse the association between periodontitis and H. pylori seropositivity (H. pylori infection). Survival analysis was performed using the NHANES III linked to mortality data. Cox proportional hazard regression was carried out to investigate the association between periodontitis and gastrointestinal tract cancer mortality in individuals with/without H. pylori infection. RESULTS: Compared to periodontal health, periodontitis was significantly associated with increased odds of H. pylori infection (OR = 1.271, 95% CI = 1.177-1.372). Periodontitis significantly increased the mortality risk from all causes (HR = 1.574, 95% CI = 1.327-1.866) and all cancers (HR = 1.948, 95% CI = 1.701-2.232), including gastrointestinal (GI) tract cancer (HR = 4.140, 95% CI = 3.656-4.687), gastric cancer (HR = 4.288, 95% CI = 3.969-4.632), and colorectal cancer (HR = 4.814, 95% CI = 3.849-6.020) in subjects with H. pylori infection after adjusting for health-related factors. Periodontitis was significantly related to the decreased survival time in subjects with GI tract (p = .001) or colorectal cancer (p = .002) and H. pylori infection. CONCLUSION: Our study demonstrated that periodontitis was significantly associated with higher mortality risk of GI tract, gastric, and colorectal cancer in subjects with H. pylori infection. Owing to an interactive effect between periodontitis and H. pylori infection on cancer mortality, H. pylori infection has a significant moderating effect in regulating the association between periodontitis and mortality due to all cancers, including GI tract cancer and colorectal cancer.

Dysregulation of the miR-30a/BiP axis by cigarette smoking accelerates oral cancer progression.

BACKGROUND: Cigarette smoking is the most significant cause of oral cancer progression. Cigarette smoke condensate (CSC) has been shown to induce endoplasmic reticulum (ER) stress. Binding immunoglobulin protein (BiP) being as an ER stress regulator, has been reported to be implicated in malignant behaviors. Therefore, the aim of this study was to investigate the role of the ER stress-responsive protein, BiP, in CSC-induced oral squamous cell carcinoma (OSCC) malignancy. METHODS: The biological role of BiP in CSC-induced tumor progression was investigated in OSCC cells (YD38 and SCC25) and in a tumor xenograft mouse model. The expressions of related genes were investigated using quantitative RT-PCR and Western blot analysis. Cell migration and invasion were assessed using scratch wound healing and Transwell invasion assays. The effects of conditioned media from OSCC cells on the angiogenic activities of endothelial cells were analyzed using a tube formation assay. The interaction between miR-30a and BiP mRNA was detected using a luciferase reporter assay. RESULTS: Our results demonstrated that CSC increased the expression of BiP in time- and dose-dependent manners in YD38 and SCC25 cells, and that silencing BiP abrogated CSC-induced cell invasion and tumor-associated angiogenesis. Notably, the putative miR-30a binding site was observed in the 3'untranslated region (UTR) of BiP mRNA, and miR-30a suppressed BiP expression by targeting 3'UTR of BiP transcript. In addition, CSC increased the expression of BiP in OSCC cells by downregulating miR-30a. We also showed that BiP promoted invasion and tumor-associated angiogenesis by increasing the production and secretion of vascular endothelial growth factor in CSC-exposed OSCC cells. Moreover, BiP inhibition suppressed OSCC growth and reduced tumor vessel density in tumor-bearing mice administered with CSC. CONCLUSIONS: These observations suggest that epigenetic regulation of BiP via miR-30a downregulation is involved in CSC-induced OSCC progression.

Associations between metabolic biomarkers and localized stage II/III periodontitis in young adults: The CHIEF Oral Health study.

AIM: To investigate the associations between metabolic risk factors and periodontitis in young adults. MATERIALS AND METHODS: The study included 1123 participants, aged 19-40 years, in Taiwan. Metabolic syndrome components were defined by the International Diabetes Federation criteria. Localized periodontitis was graded to healthy (n = 828) and stage II/III (n = 295) according to the 2017 criteria of the World Workshop. Multiple logistic regression analysis with adjustment for sex, age, betel nut consumption, and smoking were used to determine the associations. RESULTS: Greater waist circumference, serum triglycerides, and serum uric acid were associated with higher localized stage II/III periodontitis risk [odds ratio (OR) and 95% confidence interval (CI): 1.04 (1.02-1.05), 1.004 (1.002-1.006), and 1.10 (1.00-1.21), respectively]. There were no associations for total cholesterol, high-density lipoprotein, and blood pressure. There was a non-linear association between fasting glucose and localized stage II/III periodontitis, where the turning point was 105 mg/dl [OR: 0.97 (0.95-0.99) and 1.06 (1.00-1.13) when the levels were <105 and ≥105 mg/dl, respectively]. CONCLUSIONS: The risks of localized stage II/III periodontitis vary with metabolic components, in which waist circumference, serum triglycerides, and serum uric acid are the risk factors, whereas plasma glucose shows a non-linear relationship in young adults.

Recommendations for treating stage I-III periodontitis in the Taiwanese population: A consensus report from the Taiwan Academy of Periodontology.

BACKGROUND/PURPOSE: Based on the fundamental of the S3-level clinical practice guideline (CPG) for treating stage I-III periodontitis developed by the European Federation of Periodontology (EFP), this consensus report aimed to develop treatment recommendations for treating periodontitis in the Taiwanese population. METHODS: The report was constructed by experts from the Taiwan Academy of Periodontology. The following topics were reviewed: (a) the prevalence of periodontitis in Asia and current status of treatment in Taiwan; (b) specific anatomical considerations for treating periodontitis in Asians; (d) educational and preventive interventions and supragingival plaque control; (d) subgingival instrumentation and adjunctive treatment; (e) surgical periodontal therapy; and (f) maintenance and supportive periodontal care. Recommendations were made according to the evidences from the EFP CPG, the published literature and clinical studies in Asians, and the expert opinions. RESULTS: The treatment recommendations for the Taiwanese population were generally in parallel with the EFP CPG, and extra cautions during treatment and maintenance phases were advised due to the anatomical variations, such as shorter root trunk, higher prevalence of supernumerary distolingual root and lingual bony concavity in mandibular posteriors, and thinner anterior labial plate, of the Asian population. CONCLUSION: The EFP CPG could be adopted for treating periodontitis and maintaining periodontal health of the Taiwanese population, and anatomical variations should be cautious when the treatment is delivered.

Combination of a biomolecule-aided biphasic cryogel scaffold with a barrier membrane adhering PDGF-encapsulated nanofibers to promote periodontal regeneration.

OBJECTIVE AND BACKGROUND: To achieve periodontal regeneration, numerous investigations have concentrated on biomolecule supplement and optimization of bone substitute or barrier membrane. This study evaluated the benefit of combining these strategies for periodontal regeneration. METHODS: Biphasic cryogel scaffold (BCS) composed of gelatin (ligament phase) and gelatin with beta-tricalcium phosphate/hydroxyapatite (BH) (bone phase) was designed as tested bone substitute, and both enamel matrix derivatives (EMD) and bone morphogenetic protein-2 (BMP-2) were applied to formulate a biomolecule-aided BCS (BBS). Functionally graded membrane (FGM) was designed as tested barrier membrane by adhering PDGF-encapsulated poly(L-lactide-co-D/L-lactide) nanofibers on the conventional membrane (CM). BBS and FGM were characterized and tested for biocompatibility in vitro. Thirty 4 × 4 × 5 mm3 periodontal intrabony defects were created on 6 Beagle dogs. Each defect was evenly assigned to one of the following treatments including BH-CM, BCS-CM, BBS-CM, BH-FGM, BCS-FGM, and BBS-FGM, for 12 weeks. The therapeutic efficiency was assessed by micro-CT and histology. RESULTS: BCS and FGM sustained the release of biomolecules. The viability of MSCs was maintained in both phases of BCS and was promoted while seeding on the PDGF-encapsulated nanofibers. In CM-covered sites, BBS showed significantly greater osteogenesis (P < .01) and early defect fill (P < .05) relative to BH. FGM significantly promoted osteogenesis (P < .05) in BH-treated sites but showed limited benefit in BBS-treated sites. On denuded roots, cementum deposition was evident in BBS-treated sites. CONCLUSIONS: PDGF-loaded FGM promoted periodontal osteogenesis, and BBS with EMD-BMP-2 had potential for reconstructing alveolar ridge, periodontal ligament, and cementum. FGM and BBS combination provided limited additional benefit.

Association between periodontitis and pulmonary function based on the Third National Health and Nutrition Examination Survey (NHANES III).

OBJECTIVES: The purpose of this study was to investigate the association between impaired pulmonary function and periodontitis. MATERIALS AND METHODS: From the Third National Health and Nutrition Examination Survey data, we examined the association between pulmonary function and severity of periodontitis using the univariate and multivariate regression models. Moreover, the association between obstructive or restrictive spirometry patterns and periodontitis status was also determined by multivariable logistic regression analysis. RESULTS: A total of 10,645 participants were included in our study. The values of predicted FEV1%, predicted FVC%, and FEV1/FVC were found to gradually decline with increasing severity of periodontitis (p < .001). Obstructive and restrictive pulmonary functions were significantly associated with severity of periodontitis. CONCLUSION: Individuals with a greater degree of periodontitis had poor pulmonary function. However, further long-term cohort studies are required for a comprehensive evaluation.

Synthesis and Characterization of Melatonin-Loaded Chitosan Microparticles Promote Differentiation and Mineralization in Preosteoblastic Cells.

In terms of a novel scaffold with well good osteoinductive and osteoconductive capacity, melatonin (Mel) possesses positive effects on chemical linkage in scaffold structures, which may allow osteogenic differentiation. The aim of this study is to fabricate Mel-loaded chitosan (CS) microparticles (MPs) as a novel bone substitute through generating a Mel sustained release system from Mel-loaded CS MPs and evaluating its effect on the osteogenic capacity of MC3T3-E1 in vitro. The physical-chemical characteristics of the prepared CS MPs were examined by both Fourier transform infrared spectroscopy and scanning electron microscopy. The released profile and kinetics of Mel from MPs were quantified, and the bioactivity of the released Mel on preosteoblastic MC3T3-E1 cells was characterized in vitro. An in vitro drug release assay has shown high encapsulation efficiency and sustained release of Mel over the investigation period. In an osteogenesis assay, Mel-loaded CS MPs have significantly enhanced alkaline phosphatase (ALP) mRNA expression and ALP activity compared with the control group. Meanwhile, the osteoblast-specific differentiation genes, including runt related transcription factor 2 (Runx2), bone morphogentic protein-2 (Bmp2), collagen I (Col I), and osteocalcin (Ocn), were also significantly upregulated. Furthermore, quantificational alizarin red-based assay demonstrated that Mel-loaded CS MPs notably enhanced the calcium deposit of MC3T3-E1 compared with controls. In essence, Mel-loaded CS MPs can control the release of Mel for a period of time to accelerate osteogenic differentiation of preosteoblast cells in vitro.

Association between periodontitis and cognitive impairment: Analysis of national health and nutrition examination survey (NHANES) III.

OBJECTIVES: Periodontitis has been hypothesized as being one of the most common potential risk factors for the development of dementia and cognitive impairment. In order to investigate the relationship between periodontitis and cognition impairment, the National Health and Nutrition Examination Survey (NHANES) database was analysed after adjusting for potential confounding factors, including age and other systemic co-morbidities. MATERIALS AND METHODS: In total, 4,663 participants aged 20-59 years who had received full-mouth periodontal examination and undergone the cognitive functional test were enrolled. The grade of periodontal disease was categorized into severe, moderate, and mild. Cognitive function examinations, including the simple reaction time test (SRTT), symbol digit substitution test (SDST), and serial digit learning test (SDLT), were adopted for the evaluation of cognitive impairment. RESULTS: The subjects with mild and moderate to severe periodontitis had higher SDLT and SDST scores, which indicated decreased cognitive function, compared with the healthy group. After adjusting for demographic factors, education, smoking, cardiovascular diseases, and laboratory data, periodontitis was significantly correlated with elevated SDST and SDLT scores (p values for trend = 0.014 and 0.038, respectively) by generalized linear regression models. CONCLUSION: Our study highlighted that periodontal status was associated with cognitive impairment in a nationally representative sample of US adults.

A novel 3D-printed computer-assisted piezocision guide for surgically facilitated orthodontics.

Surgical interventions on the alveolar ridges aimed at facilitating orthodontic tooth movement have been extensively reported. However, unexpected events or complications still occur in daily practice. The purpose of this report was to present a novel 3-dimensional (3D) computer-assisted piezocision guide (CAPG) designed to be translucent for increased visibility, rigid for enhanced support during guidance, and porous for profuse irrigation during procedure. Such a design can function to minimize the risk of surgical complications. In this case, we present a novel 3D-printed CAPG to facilitate a minimally invasive periodontal accelerated osteogenic orthodontics (PAOO) procedure with a guide that provides accuracy, adequate visibility, and greater access for the coolant to reach the surgery site. By navigating the cone-beam computed tomography data, we precisely know the cortical bone thickness, root direction, and interrelations between anatomic structures in an individual situation, which allows us to design our cutting slot for the required length and depth according to the operator's knowledge. Finally, 3D printing was applied, transferring our surgical plan to fabricate the CAPG. Moreover, the well designed pores on the CAPG allow effective irrigation during the piezocision procedure. This minimally invasive procedure was uneventful, and no devitalized tooth or alveolar bone was found.

Are Chronic Periodontitis and Gingivitis Associated with Dementia? A Nationwide, Retrospective, Matched-Cohort Study in Taiwan.

BACKGROUND: Chronic periodontitis and gingivitis are associated with various diseases; however, their impact on dementia is yet to be elucidated. This study is aimed at investigating the association between chronic periodontitis and gingivitis, and the risk of developing dementia. METHODS: A total of 2,207 patients, with newly diagnosed chronic periodontitis and gingivitis between January 1, 2000 and December 31, 2000, were selected from the National Health Insurance Research Database of Taiwan, along with 6,621 controls matched for sex and age. After adjusting for confounding factors, Cox proportional hazards analysis was used to compare the risk of developing dementia during the 10-year follow-up period. RESULTS: Of the study subjects, 25 (1.13%) developed dementia compared to 61 (0.92%) in the control group. Cox proportional hazards regression analysis revealed that the study subjects were more likely to develop dementia (hazard ratio (HR) 2.085, 95% CI 1.552-4.156, p < 0.001). After adjusting for sex, age, monthly income, urbanization level, geographic region, and comorbidities, the HR for dementia was 2.54 (95% CI 1.297-3.352, p = 0.002). CONCLUSIONS: Patients with chronic periodontitis and gingivitis have a higher risk of developing dementia. However, further studies on other large or national data sets are required to support the current findings.

The association between temporomandibular disorders and joint hypermobility syndrome: a nationwide population-based study.

OBJECTIVES: This study aims to investigate the risk factors of temporomandibular disorders (TMDs), including disc or non-disc-related disorders, and joint hypermobility syndrome (JHS) retrospectively and to analyze the factors by estimating the magnitude of the association between the two conditions using a nationwide population-based dataset. MATERIALS AND METHODS: A total of 975,788 eligible patients' de-identified data were obtained from a representative database composed of one million of Taiwan's population since 2004 to 2008. All associated factors, such as gender, age, facial trauma, and psychosis, which correlated with TMDs and JHS were examined. Multiple logistic regression modeling adjusted for confounding variables to determine the odds ratio of variables that made an important contribution to TMDs and JHS. RESULTS: For all TMDs patients, only 1.47% patients had disc-related disorders. For all JHS patients, only 3.85% patients are diagnosed with concomitant TMDs. Statistically significant association was observed between joint hypermobility and TMDs. Furthermore, the prevalence of JHS patients shows significant difference within TMD subgroups, in which 9.52% of JHS patients have disc disorders and 90.48% of JHS patients do not. All associated factors, such as gender, age, JHS, facial trauma, and psychosis, had a significant impact on the TMDs. Interestingly, patients with TMJ articular disc disorders are 6.7 times more likely to be diagnosed with JHS compared to patients without disc-related disorders. CONCLUSIONS: Our results confirm that there is a significant positive association between TMDs and JHS, highlighting that patients with disc-related TMDs are more likely to experience JHS than patients with TMDs without disc disorders. CLINICAL RELEVANCE: Individuals with TMD associated with JHS should be carefully evaluated by inter-disciplinary specialists as these factors may eventually have impact on the prognosis of TMDs and JHS.

Tumor-associated macrophages promote oral cancer progression through activation of the Axl signaling pathway.

BACKGROUND: Recent studies suggest that tumor-associated macrophages (TAMs) promote tumor growth and metastasis. Our previous report demonstrated that Axl signaling promotes carcinogenesis and progression of oral squamous cell carcinoma (OSCC). This study aims to test the potential involvement of growth arrest-specific gene 6 (Gas6)/Axl signaling in the protumoral effect of TAMs. METHODS: Co-culture experiments by incubation of OSCC cells (YD38 and OE) and macrophages (THP-1) were performed. The expression of Gas6/Axl and epithelial-mesenchymal transition (EMT) genes were examined in YD38 and OE cells. The effect of Gas6/Axl signaling on co-cultured cancer cells was further investigated by knocking down Axl expression and neutralizing Gas6. Axl and TAM distribution were analyzed by immunohistochemistry in OSCC tissues. RESULTS: Activation of Axl signaling and increased expression of mesenchymal markers, along with increased invasion/migration ability of OSCC cells, was noted upon co-culture with THP-1. Neutralization of Gas6 in the co-culture system or knockdown of Axl in YD38 caused the co-culture effects to be diminished. Co-culture with THP-1 increased nuclear factor (NF)-κB nuclear translocation and transcription activity in YD38 cells. A significant association between the TAM count and expression of phosphorylated Axl (P = 0.004) was found in vivo cancer tissues. CONCLUSIONS: TAMs play a protumor role in OSCC and likely promote tumor progression through activation of the Gas6/Axl-NF-κB signaling pathway. Therefore, Gas6/Axl and NF-κB signaling in OSCC cells may be a putative target for therapeutic intervention.

Protumoral effect of macrophage through Axl activation on mucoepidermoid carcinoma.

OBJECTIVE: This study aims to test the potential involvement of Axl signaling in the protumoral effect of tumor-associated macrophages (TAMs) in mucoepidermoid carcinoma (MEC). MATERIALS AND METHODS: We carried out cocultured experiments by incubation of MEC cells (UTMUC-1) and macrophages (THP-1) and examined Axl activation status. The expression of MMPs and behavior change were examined in UT-MUC-1 cells. The effect of Axl signaling on co-cultured cancer cells was further investigated by knockdown Axl expression and suppression by Axl-specific inhibitor R428. RESULTS: Activation of Axl signaling and increased expression and activity of MMP-2 and MMP-9 along with increased invasion/migration ability in MEC cells were observed when co-cultured with TAMs. Upon knockdown of Axl in MEC or addition of R428 in the co-cultured system, these co-cultured effects were diminished. CONCLUSION: TAMs play a protumoral role in MEC via activation of the Axl signaling pathway, up-regulating MMPs expression, and increasing invasion/migration ability.