Linking periodontitis with 20 cancers, emphasis on oropharyngeal cancer: a Mendelian randomization analysis.

While associations between periodontitis and an elevated risk of cancer have been suggested, the results of existing observational studies have been inconsistent, also leaving room for further investigation into the underlying mechanisms. This study was designed to delve into the possible causal link between periodontitis and 20 standard cancers while concurrently identifying potential mediators. We initiated a Mendelian randomization analysis that drew from either publicly accessible or personally obtained genome-wide association study (GWAS) datasets. The inverse variance weighting (IVW) method served as our primary tool for analysis. To ensure the strength and consistency of our results, we implemented additional strategies, including weighted median, weighted mode, MR-Egger regression, and MR pleiotropy residual sum and outlier (MR-PRESSO), bolstered by funnel plots. Our analysis unveiled an elevated risk of head and neck cancer concomitant with periodontitis (p = 0.041, OR 0.999, 95% CI 0.999-1.000), specifically a heightened risk of oropharyngeal cancer (p = 0.022, OR 0.999, 95% CI 0.999-1.000). As a result of probing into potential mediators, Fusobacterium nucleatum emerged as a likely intermediary in the promoting effect of periodontitis on oropharyngeal cancer (p = 0.021, OR 0.999, 95% CI 0.998-1.000). Inversely, basal cell carcinoma and endometrial cancer demonstrated an association with an increased incidence of periodontitis (basal cell carcinoma: p = 0.020, OR 0.987, 95% CI 0.976-0.998; endometrial cancer: p = 0.027, OR 0.984, 95% CI 0.970-0.998). However, periodontitis exerted no significant causal impact on the 19 other common cancers or the three subtypes of head and neck cancer. To conclude, our results support the theory that periodontitis contributes to an enhanced risk of head and neck cancer, particularly oropharyngeal cancer, with Fusobacterium nucleatum functioning as a potential intermediary.

Bone Regeneration Facilitated by Autologous Bioscaffold Material: Liquid Phase of Concentrated Growth Factor with Dental Follicle Stem Cell Loading.

The application of bioengineering techniques for achieving bone regeneration in the oral environment is an increasingly prominent field. However, the clinical use of synthetic materials carries certain risks. The liquid phase of concentrated growth factor (LPCGF), as a biologically derived material, exhibits superior biocompatibility. In this study, LPCGF was employed as a tissue engineering scaffold, hosting dental follicle cells (DFCs) to facilitate bone regeneration. Both in vivo and in vitro experimental results demonstrate that this platform significantly enhances the expression of osteogenic markers in DFCs, such as alkaline phosphatase (ALP), runt-related transcription factor 2 (Runx2), and type I collagen (Col1a1). Simultaneously, it reduces the expression of inflammation-related genes, particularly interleukin-6 (IL-6) and interleukin-8 (IL-8), thereby alleviating the negative impact of the inflammatory microenvironment on DFCs. Further investigation into potential mechanisms reveals that this process is regulated over time by the WNT pathway. Our research results demonstrate that LPCGF, with its favorable physical characteristics, holds great potential as a scaffold. It can effectively carry DFCs, thereby providing an optimal initial environment for bone regeneration. Furthermore, LPCGF endeavors to closely mimic the mechanisms of bone healing post-trauma to facilitate bone formation. This offers new perspectives and insights into bone regeneration engineering.

Efficacy of Music Intervention for Dental Anxiety Disorders: A Systematic Review and Meta-Analysis.

Objective To evaluate the effectiveness of music therapy for dental anxiety disorders. Methods In order to gather clinical randomized controlled trials comparing the effectiveness of music interventions to traditional oral manipulation in patients with dental anxiety disorders, computer searches of the electronic databases of Wanfang, CNKI, VIP, PubMed, Web of Science, ScienceDirect, Cochrane library, Scopus, and CINAHL were conducted. The search period covered from 23 December 2022, through to the development of the database. The Cochrane Handbook was used to assess the quality of the included literature, and two researchers independently conducted the literature screening and data extraction. Stata 17.0 and RevMan 5.3 were used to conduct the meta-analysis. Results The preoperative baseline levels of the music intervention group were similar to those of the control group (p > 0.05), according to the meta-analysis, and music intervention significantly decreased heart rate (I2 = 81.2%, WMD (95% CI): -7.33 (-10.07, -4.58), p < 0.0001), systolic blood pressure fluctuations (I2 = 85.6%, WMD (95% CI): -6.10(-9.25, 2.95), p < 0.0001), diastolic blood pressure (I2 = 79.7%, WMD (95% CI): -4.29(-6.57, -2.02), p < 0.0001) fluctuations, anxiety scores (I2 = 19.6%, WMD (95% CI): -9.04(-11.45, 6.63), p < 0.0001), and pain scores (I2 = 32.7%, WMD (95% CI): -7.64(-9.43, -5.85), p < 0.0001), as well as significantly lowered anxiety and pain levels and raised patients' cooperation rates (I2 = 0%, OR (95% CI): 3.03(1.24, 7.40), p = 0.02). Conclusions Music interventions are effective for dental anxiety disorders, but given the limitations of the study, more multicenter, large-sample, high-quality randomized controlled trials are needed to further validate the findings and obtain more objective and reliable clinical evidence.

Automatic Registration of Homogeneous and Cross-Source TomoSAR Point Clouds in Urban Areas.

Building reconstruction using high-resolution satellite-based synthetic SAR tomography (TomoSAR) is of great importance in urban planning and city modeling applications. However, since the imaging mode of SAR is side-by-side, the TomoSAR point cloud of a single orbit cannot achieve a complete observation of buildings. It is difficult for existing methods to extract the same features, as well as to use the overlap rate to achieve the alignment of the homologous TomoSAR point cloud and the cross-source TomoSAR point cloud. Therefore, this paper proposes a robust alignment method for TomoSAR point clouds in urban areas. First, noise points and outlier points are filtered by statistical filtering, and density of projection point (DoPP)-based projection is used to extract TomoSAR building point clouds and obtain the facade points for subsequent calculations based on density clustering. Subsequently, coarse alignment of source and target point clouds was performed using principal component analysis (PCA). Lastly, the rotation and translation coefficients were calculated using the angle of the normal vector of the opposite facade of the building and the distance of the outer end of the facade projection. The experimental results verify the feasibility and robustness of the proposed method. For the homologous TomoSAR point cloud, the experimental results show that the average rotation error of the proposed method was less than 0.1°, and the average translation error was less than 0.25 m. The alignment accuracy of the cross-source TomoSAR point cloud was evaluated for the defined angle and distance, whose values were less than 0.2° and 0.25 m.

Cryptotanshinone inhibits oral squamous cell carcinoma through the autophagic pathway.

Oral squamous cell carcinoma (OSCC) is one of the most common malignant tumors with a low quality of life. Because traditional surgical treatment often causes large wounds and then affects the quality of life of patients, it is urgent to find new and efficient drugs with good safety for clinical treatment. This study aimed to identify potential anticancer drugs starting from the traditional Chinese medicine Salvia miltiorrhiza extract. Cryptotanshinone, a compound isolated from the Chinese herb Salvia miltiorrhiza, was found to significantly induce apoptosis and inhibit proliferation in OSCC. By electron microscopy, autophagosomes were found. Confocal fluorescence microscopy data showed that cryptotanshinone significantly induced autophagy in OSCC cells. Mechanistically, the western blot assay indicated that cryptotanshinone induced cell autophagy through the activation of the LC3 pathway, whereas the autophagy inhibitor 3-methyladenine attenuated these effects. Furthermore, we demonstrated that cryptotanshinone had a significant antitumor effect in a tumor xenograft model, and no damage to vital organs was observed. Our findings provide evidence that cryptotanshinone may be a novel therapeutic strategy for the treatment of OSCC.

Peptide decorated demineralized dentin matrix with enhanced bioactivity, osteogenic differentiation via carboxymethyl chitosan.

OBJECTIVES: To improve the biocompatibility and osteogenic activity of demineralized dentin matrix (DDM) by grafting peptides on its surface. METHODS: DDM was obtained by pulverizing extracted human teeth that had been systematically demineralized and dried. Four groups of materials were evaluated: DDM, DDM/carboxymethyl chitosan (CMC), DDM/CMC/bone forming peptide-1 (BFP-1), and blank. X-ray photoelectron spectroscopy (XPS), Fourier transform infrared spectroscopy (FT-IR) and fluorescence localization were used to characterize the surface of the DDM materials. Cell viability was assessed using a CCK8 assay, scanning electron microscopy (SEM) and in vitro osteogenesis was analyzed using real-time RT-PCR (RT-qPCR) and Alizarin red and alkaline phosphatase staining. Three different materials were implanted into mandibular bone defects in rats. After 8 weeks, bone regeneration was assessed by histomorphometry of HE-stained slides. RESULTS: FT-IR, XPS, and fluorescence microscopy demonstrated that the DDM surfaces were successfully modified with BFP-1. The CCK8 assay indicated that the proliferation of cells is higher on the DDM/CMC/BFP-1 material than on DDM or DDM/CMC (P < 0.05). Cells were more likely to adhere to DDM/CMC/BFP-1, as observed by SEM. Greater in vitro osteogenesis was observed in the DDM/CMC/BFP-1 group which displayed stronger alkaline phosphatase activity, more alizarin red-stained nodules, and higher target gene expression, as detected by RT-qPCR (P＜0.05). HE staining of in vivo explants indicated that greater quantities of new bone had formed in the DDM/CMC/BFP-1 group. SIGNIFICANCE: Compared with DDM, DDM/CMC/BFP-1 exhibited superior biocompatibility and osteogenesis, using a method of surface modification that has great potential for future clinical use.

TNF­α regulates the osteogenic differentiation of bone morphogenetic factor 9 adenovirus­transduced rat follicle stem cells via Wnt signaling.

Periodontitis is a chronic infectious disease that alters the cellular microenvironment and promotes bone absorption. Bone morphogenetic protein 9 (BMP9) serves an important role in proliferation and differentiation, and tumor necrosis factor­alpha (TNF­α) is an important contributor to bone resorption. The present study aimed to investigate the effect of osteogenic differentiation in the presence of BMP9 and TNF­α in rat follicle stem cells (rDFCs). rDFCs were transfected with adenoviruses expressing BMP9 (AdBMP9) and the expression levels of important proteins [BMP9, ß­catenin, glycogen synthase kinase 3ß (GSK3ß), phosphorylated­GSK3ß, calcium/calmodulin dependent protein kinase II and nemo like kinase] were determined using western blotting. The effect of osteogenesis was analyzed using reverse transcription­quantitative PCR, in addition to alkaline phosphatase, Alizarin Red S, and hematoxylin and eosin staining methods. The results of the present study revealed that TNF­α activated the canonical Wnt signaling pathway and suppressed osteogenesis. High concentrations of Dickkopf 1 (DKK1) reduced the osteogenic differentiation of AdBMP9­transduced rDFCs, whereas low concentrations of DKK1 promoted BMP9­induced bone formation, which was discovered to partially act via the canonical and non­canonical Wnt signaling pathways. In conclusion, the findings of the present study suggested that the enhanced promoting effect of BMP9 alongside the treatment with low concentrations of DKK1 may be useful for treating periodontitis bone absorption.

DKK1 and TNF-alpha influence osteogenic differentiation of adBMP9-infected-rDFCs.

OBJECTIVES: Rat dental follicle cells (rDFCs) function as precursor cells of periodontal tissues. Bone morphogenetic protein (BMP9) plays an important role in proliferation and differentiation. Tumour necrosis factor-alpha (TNF-alpha) is an important contributor to bone resorption. Wnt canonical pathway can be inhibited by Dickkopf 1 (DKK1). The aim of the study was to enhance the osteogenesis of BMP9 treated rDFCs in an inflammatory environment and elucidate the mechanism. MATERIALS AND METHODS: rDFCs were infected by adenoviruses expressing BMP9 (adBMP9). Expression levels of proteins and genes were measured by Western blotting and qPCR. The effect on osteogenesis was evaluated by measuring the activity of alkaline phosphatase (ALP), observation of Alizarin Red S and haematoxylin and eosin staining. RESULTS: TNF-alpha activated the canonical Wnt pathway and inhibited the non-canonical pathway. DKK1 suppressed the canonical pathway and promoted the non-canonical pathway. Addition of TNF-alpha or DKK1 inhibited BMP9/Smad pathway. However, this inhibition was reduced by the addition of DKK1 with TNF-alpha. CONCLUSIONS: DKK1 reduces the inhibitory effects of TNF-alpha in adBMP9-infected-rDFCs, possibly through interaction with the Smad signalling pathway and Wnt pathways. These findings may lead to a novel approach for the treatment of periodontitis-related alveolar bone defects.

Glutathione S-transferase mu-1, glutathione S-transferase theta-1 null genotypes, and oral cancer risk: A meta-analysis in the Chinese population.

AIM OF STUDY: Several studies have evaluated the correlation between glutathione S-transferase mu-1 (GSTM1), GST theta-1 (GSTT1) polymorphisms and oral cancer in Chinese people. However, the results are inconsistent. To assess the effects of GSTM1, GSTT1 null genotypes on the risk for development of oral cancer in the Chinese population, a meta-analysis was performed. MATERIALS AND METHODS: Studies were identified using PubMed and Chinese databases through February 2016. The associations were assessed with pooled odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: This meta-analysis included six studies with 1306 oral cancer cases and 1484 controls. In the overall analysis, no significant association between GSTM1, GSTT1 polymorphisms and oral cancer was found in the Chinese population. In the subgroup analyses by geographic areas and source of controls, significant risk was found between GSTM1 null genotype and oral cancer in Mainland China (OR = 2.715, 95% CI = 2.17-3.38), but not in Taiwan China. CONCLUSION: Our meta-analysis suggested that GSTM1 null genotype might be associated with an increased risk of developing oral cancer in individuals from Mainland China.

Tanshinone IIA induces cell death via Beclin-1-dependent autophagy in oral squamous cell carcinoma SCC-9 cell line.

Tanshinone IIA (TAN) is one of the major functional compounds of Salvia miltiorrhiza Bunge and possesses the ability to suppress the growth of multiple cancer cell types via its apoptosis- and autophagy-inducing functions. In this study, the effect of TAN therapy on the survival of oral squamous cell carcinoma (OSCC) was evaluated, and the underlying mechanism involved in the treatment was investigated. Human oral squamous cell carcinoma cell SCC-9 was used for in vitro assays and induction in an OSCC xenograft mouse model. The tumor cells were subjected to TAN administration at different concentrations. Then the apoptosis and autophagy processes in SCC-9 cells were evaluated and the activities of Beclin-1/Atg7/Atg12-Atg5 and PI3K/Akt/mTOR pathways were determined. In addition, by knocking down the expression of Beclin-1 in SCC-9 cells, the study also assessed the role of the indicator in the anti-OSCC effect of TAN. Results of in vitro assays were further validated with an OSCC xenograft mouse model. Administration of TAN-induced cell apoptosis and upregulated the expression of cleaved-caspase-3. Simultaneously, the autophagy process in SCC-9 cells was initiated by TAN, which was signaled by the formation of autophagosomes and increase in the ratio of LC3 II/LC3I. The above processes were associated with the activation of Beclin-1/Atg7/Atg12-Atg5 signaling and inhibition of PI3K/Akt/mTOR signaling. Our results also inferred a partially Beclin-1-dependent mechanism of action of TAN in OSCC cells: knockdown of the Beclin-1 blocked the effect of TAN on SCC-9 cells both in vivo and in vitro. Our study provided a preliminary explanation of the mechanism involved in TAN effect: the agent exerted its autophagy-inducing effect against OSCC in a multipronged manner, by both inducing the Beclin-1/Atg7/Atg12-Atg5 pathway and suppressing the PI3K/Akt/mTOR pathway.

The healing of alveolar bone defects with novel bio-implants composed of Ad-BMP9-transfected rDFCs and CHA scaffolds.

Cells, scaffolds, and growth factors play important roles in bone regeneration. Bone morphogenetic protein 9 (BMP9), a member of BMP family, could facilitate osteogenesis by regulating growth factors and promoting angiogenesis. Similar to other stem cells, rat dental follicle stem cells (rDFCs), the precursor cells of cementoblasts, osteoblasts and periodontal ligament cells, can self-renew and exhibit multipotential capacity. Coralline hydroxyapatite (CHA) has good biocompatibility and conductivity required for bone tissue engineering. Here, we reported that BMP9 could enhance the osteogenic differentiation of rDFCs in cell culture. Moreover, our results suggested that BMP9 acted through the Smad1/5/8 signaling pathway. We also produced a novel scaffold that encompasses bio-degradable CHA seeded with recombinant adenoviruses expressing BMP9-transfected rDFCs (Ad-BMP9-transfected rDFCs). With this implant, we achieved more alveolar bone regeneration in the alveolar bone defect compared to blank group, CHA group and rDFCs group. Our results provided a novel bio-implants composed of Ad-BMP9-transfected rDFCs and CHA scaffolds and its mechanism is regarding the activation of Smad1/5/8 signaling pathway in BMP9-induced rDFCs osteogenesis.

[Survey on dental caries status of migrant children aged 6-12 years in Minhang district of Shanghai].

PURPOSE: To investigate the prevalence of dental caries among migrant children aged 6-12 years in Minhang district of Shanghai, so as to provide some basic data for children health care. METHODS: Ten thousand and eleven school children in 8 primary schools of Minhang district of Shanghai were investigated by cluster random sampling. Visual examination combined with probe inspection was used to diagnose caries, and then rate of caries and DMFT (decayed，missing and filled teeth) were calculated. SPSS 13.0 software package was used for statistical analysis. RESULTS: The prevalence of caries among children aged 6-12 years was 67.07%, which was significantly higher than that in children from government-owned schools (61.99%)(P<0.01). The prevalence of caries was 75.82% in 6-year-old group and highest compared to other groups. CONCLUSIONS: It can't be optimistic about the caries prevalence among migrant children aged 6-12 years in Minhang district，Shanghai.More attentions should be payed in prevention and early intervention of dental caries for children above 6 years old.

Prevalence and care index of early childhood caries in mainland China: evidence from epidemiological surveys during 1987-2013.

Early childhood caries (ECC) is the most common chronic disease in young children. Its reported prevalence varies greatly across China. This systematic review aimed to explore the epidemiological characteristics of ECC in mainland China from 1987 to 2013. In total, 102 articles were included. The pooled national prevalence and care index (ft/dmft%) for ECC were 65.5% and 3.6%, respectively. The overall ECC prevalence declined from 77.9% during 1987-1994 to 56.4% during 2010-2013. The pooled ECC prevalence for children aged 1-6 years was 0.3%, 17.3%, 40.2%, 54.4%, 66.1%, and 70.7%, respectively. There was no significant difference in prevalence between boys (59.1%) and girls (58.9%); and the care index was also similar (8.1% versus 7.7%). Slightly higher ECC prevalence was observed in rural areas (63.5%) compared with urban areas (59.5%) (RR = 1.08, 95% CI: 1.02-1.14); but a much higher care index was reported in urban children (6.0%) than their rural counterparts (1.6%) (RR = 3.68, 95% CI: 2.54-5.35). The 2006-2013 map of ECC prevalence among 5-year-olds showed wide geographic variations across China. Four adjacent provinces, including Sichuan, Chongqing, Hubei, and Shaanxi, constituted the areas with the lowest ECC prevalence in mainland China.

Bone morphogenetic protein-9 induces PDLSCs osteogenic differentiation through the ERK and p38 signal pathways.

Periodontal ligament stem cells (PDLSCs) with bone morphogenic ability are used to treat diseases such as periodontitis. Their treatment potential is increased when used in combination with proteins that induce osteogenic differentiation. For example, bone morphogenetic protein-9 (BMP9) has been found to have potent osteogenic activity. In the present study, PDLSCs were isolated from human periodontal membrane and infected with recombinant adenoviruses expressing BMP9 (Ad-BMP9). Levels of osteogenic markers such as runt-related transcription factor 2 (Runx2), alkaline phosphatase (ALP), osteopontin (OPN), and osteocalcin (OCN) as well as mineralization ability were measured. The results showed that BMP9 promoted bone formation of PDLSCs. In other experiments, SB203580 and PD98059, which are inhibitors of p38 and ERK1/2, respectively, were used to determine if these kinases are involved in the osteogenic differentiation process. The resulting protein expression profiles and osteogenic markers of PDLSCs revealed that the mitogen-activated protein kinase (MAPK) signaling pathway might play an important role in the process of BMP9-induced osteogenic differentiation of PDLSCs.

[Investigation of accuracy of premolar length measured by cone beam CT in vivo].

OBJECTIVE: To investigate the feasibility and accuracy of length measurement of in vivo teeth by using cone beam CT (CBCT). METHODS: Before orthodontic extraction, 109 vital premolars from 40 participants were scanned by using CBCT and reconstructed by using InVivoDental software. Buccal-lingual sectional images along the long axis of teeth were then acquired, and the crown, root, and tooth length were measured separately. After careful extraction and fixation, the corresponding length of the same tooth was measured by using a digital caliper. CBCT measurement accuracy was then verified by using physical measurements as reference. RESULTS: CBCT and the physical method did not obtain significantly different measurements of the root, crown, and tooth length of experimental teeth (P=0.790, P=0.621, P=0.657, respectively), and the measurements were found to be consistent. The 95% limits of agreement of root, crown, and tooth length were -1.10 mm to 1.13 mm, -1.00 mm to 0.96 mm, and -1.00 mm to 1.05 mm, respectively. CONCLUSION: The difference between CBCT and the physical method was not significant, and good consistency was shown. CBCT could be applied in noninvasive measurement of in vivo teeth.

Bone morphogenetic protein-9 induces osteogenic differentiation of rat dental follicle stem cells in P38 and ERK1/2 MAPK dependent manner.

Dental follicle stem cells are a group of cells possessing osteogenic, adipogenetic and neurogenic differentiations, but the specific mechanism underlying the multilineage differentiation remains still unclear. Great attention has been paid to bone morphogenetic protein-9 (BMP-9) due to its potent osteogenic activity. In the present study, rat dental follicle stem cells were isolated and purified, and cells of passage 3 underwent adenovirus mediated BMP-9 gene transfection to prepare dental follicle stem cells with stable BMP-9 expression. Detection of alkaline phosphatase (ALP) and calcium deposition showed dental follicle stem cells transfected with BMP-9 gene could significantly promote the osteogenesis. In addition, SB203580 and PD98059 were employed to block the p38 mitogen-activated protein kinase (p38MAPK) and extracellular signal-regulated kinase (ERK1/2), respectively. Detection of ALP and calcium deposition revealed the BMP-9 induced osteogenic differentiation of dental follicle stem cells depended on MAPK signaling pathway.