Design, synthesis, and evaluation of benzodioxolane compounds for antitumor activity.

This study reports the design, synthesis, and comprehensive biological evaluation of 13 benzodioxolane derivatives, derived from the core structure of piperine, a natural product with established antitumor properties. Piperine, primarily found in black pepper, has been noted for its diverse pharmacological activities, including anti-inflammatory, antioxidant, and anticancer effects. Leveraging piperine's antitumor potential, we aimed to enhance its efficacy through structural modifications. Among the synthesized compounds, HJ1 emerged as the most potent, exhibiting a 4-fold and 10-fold increase in inhibitory effects on HeLa and MDA-MB-231 cell lines, respectively, compared to piperine. Furthermore, HJ1 demonstrated a favorable safety profile, characterized by significantly lower cytotoxicity towards the human normal cell line 293T. Mechanistic investigations revealed that HJ1 markedly inhibited clonogenicity, migration, and adhesion of HeLa cells. In vivo studies utilizing the chick embryo chorioallantoic membrane (CAM) model substantiated the robust antitumor activity of HJ1, evidenced by its ability to suppress tumor angiogenesis and reduce tumor weight. These results suggest that HJ1 holds significant promise as a lead compound for the development of novel antitumor therapies.

Oral microbiome associated with differential ratios of Porphyromonas gingivalis and Streptococcus cristatus.

Periodontitis has recently been defined as a dysbiotic disease caused by an imbalanced oral microbiota. The transition from commensal microbial communities to periodontitis-associated ones requires colonization by specific pathogens, including Porphyromonas gingivalis. We previously reported an antagonistic relationship between Streptococcus cristatus and P. gingivalis. To determine the role of S. cristatus in altering the interactions of P. gingivalis with other oral bacteria in a complex context, we collected dental plaque samples from patients with periodontitis and assigned them to two groups based on the ratios of S. cristatus and P. gingivalis. We then characterized the microbial profiles of the dental plaque samples using shotgun metagenomic sequencing and compared the oral microbial composition and functional capabilities of the group with high S. cristatus-P. gingivalis ratios with the low ratio group. Taxonomic annotation revealed significant differences in the microbial composition at both the genus and species levels between the low and high S. cristatus-P. gingivalis ratio groups. Notably, a higher microbial diversity was observed in the samples with low S. cristatus-P. gingivalis ratios. Furthermore, the antibiotic resistance gene profiles of the two groups were also distinct, with a significantly increased abundance of the genes in the dental plaque samples with low S. cristatus-P. gingivalis ratios. It, therefore, indicates that the S. cristatus-P. gingivalis ratios influenced the virulence potential of the oral microbiome. Our work shows that enhancing the S. cristatus-P. gingivalis ratio in oral microbial communities can be an attractive approach for revising the dysbiotic oral microbiome.IMPORTANCEPeriodontitis, one of the most common chronic diseases, is linked to several systemic diseases, such as cardiovascular disease and diabetes. Although Porphyromonas gingivalis is a keystone pathogen that causes periodontitis, its levels, interactions with accessory bacteria and pathobionts in the oral microbiome, and its association with the pathogenic potential of the microbial communities are still not well understood. In this study, we revealed the role of Streptococcus cristatus and the ratios of S. cristatus and P. gingivalis in modulating the oral microbiome to facilitate a deeper understanding of periodontitis and its progression. The study has important clinical implications as it laid a foundation for developing novel non-antibiotic therapies against P. gingivalis and improving the efficiency of periodontal treatments.

Oral microbiome associated with differential ratios of Porphyromonas gingivalis and Streptococcus cristatus.

Background: Periodontitis has been recently defined as a dysbiotic disease resulting from imbalanced oral microbiota. The transition of microbial communities from commensal to periodontitis-associated ones likely requires colonization by specific pathogens, including Porphyromonas gingivalis. We previously reported an antagonistic relationship between Streptococcus cristatus and P. gingivalis and the role of S. cristatus in inhibition of the biofilm formation, invasion, and gingipain enzymatic activity of P. gingivalis. Given the importance of P. gingivalis as a keystone pathogen of polymicrobial communities, the determinants of P. gingivalis levels, its interaction with the core microbiota, and association with the pathogenic potential of the microbial communities need to be addressed. Results: This present study intends to determine the role of S. cristatus in altering interactions of P. gingivalis with other oral bacteria in a complex context. We collected dental plaque samples from periodontitis patients and assigned them into two groups based on their ratios of S. cristatus and P. gingivalis. We then characterized microbial profiles of the dental plaque samples using shotgun metagenomic sequencing and subsequently compared oral microbial composition and functional capabilities between groups with high or low S. cristatus-P. gingivalis ratios. Taxonomic annotation showed significant differences in microbial compositions at both genus and species levels between the two groups. Notably, a higher microbial composition diversity was observed in the samples with low S. cristatus-P. gingivalis ratios. The antibiotic resistance gene profiles of the two groups are also distinct, with significantly increased diversity and abundance of antibiotic resistance genes in the dental plaque samples with low S. cristatus-P. gingivalis ratios, which likely lead to elevated virulence potential. Conclusions: Overall, our work highlights the importance of S. cristatus-P. gingivalis ratios in influencing the virulence of the oral microbiome. Approaches to enhance S. cristatus-P. gingivalis ratios in oral microbial communities will be attractive for revising the dysbiotic oral microbiome.

Influences of race/ethnicity in periodontal treatment response and bacterial distribution, a cohort pilot study.

Objectives: Periodontitis disproportionately affects different racial and ethnic populations. We have previously reported the higher levels of Porphyromonas gingivalis and lower ratios of Streptococcus cristatus to P. gingivalis may contribute to periodontal health disparities. This prospective cohort study was designed to investigate if ethnic/racial groups responded differently to non-surgical periodontal treatment and if the treatment outcomes correlated to the bacterial distribution in patients with periodontitis before treatment. Methods: This prospective cohort pilot study was carried out in an academic setting, at the School of Dentistry, University of Texas Health Science Center at Houston. Dental plaque was collected from a total of 75 African Americans, Caucasians and Hispanics periodontitis patients in a 3-year period. Quantitation of P. gingivalis and S. cristatus was carried out using qPCR. Clinical parameters including probing depths and clinical attachment levels were determined before and after nonsurgical treatment. Data were analyzed using one-way ANOVA, the Kruskal-Wallis test, the paired samples t-test and the chi-square test. Results: The gains in clinical attachment levels after treatment significantly differed amongst the 3 groups-Caucasians responded most favorably, followed by African-Americans, lastly Hispanics, while numbers of P. gingivalis were highest in Hispanics, followed by African-Americans, and lowest in Caucasians (p = 0.015). However, no statistical differences were found in the numbers of S. cristatus amongst the 3 groups. Conclusion: Differential response to nonsurgical periodontal treatment and distribution of P. gingivalis are present in different ethnic/racial groups with periodontitis.

Identification of microbiological factors associated with periodontal health disparities.

The present study aimed at identifying risk factors associated with periodontitis development and periodontal health disparities with emphasis on differential oral microbiota. The prevalence of periodontitis is recently rising dentate adults in the US, which presents a challenge to oral health and overall health. The risk of developing periodontitis is higher in African Americans (AAs), and Hispanic Americans (HAs) than in Caucasian Americans (CAs). To identify potentially microbiological determinations of periodontal health disparities, we examined the distribution of several potentially beneficial and pathogenic bacteria in the oral cavities of AA, CA, and HA study participants. Dental plaque samples from 340 individuals with intact periodontium were collected prior to any dental treatment, and levels of some key oral bacteria were quantitated using qPCR, and the medical and dental histories of participants were obtained retrospectively from axiUm. Data were analyzed statistically using SAS 9.4, IBM SPSS version 28, and R/RStudio version 4.1.2. Amongst racial/ethnic groups: 1) neighborhood medium incomes were significantly higher in the CA participants than the AA and the HA participants; 2) levels of bleeding on probing (BOP) were higher in the AAs than in the CAs and HAs; 3) Porphyromonas gingivalis levels were higher in the HAs compared to that in the CAs; 4) most P. gingivalis detected in the AAs were the fimA genotype II strain that was significantly associated with higher BOP indexes along with the fimA type IV strain. Our results suggest that socioeconomic disadvantages, higher level of P. gingivalis, and specific types of P. gingivalis fimbriae, particularly type II FimA, contribute to risks for development of periodontitis and periodontal health disparities.

Features of gastric cancer by anatomic subsite in northern China: A multi-center Health Science Report database study.

BACKGROUND: The features of gastric cancer based on the anatomic site remain unknown in northern China patients. AIM: To analyze gastric cancer features and associated trends based on the anatomical site in northern China patients. METHODS: This cross-sectional study used incident gastric cancer case data from 10 Peking University-affiliated hospitals (2014 to 2018). The clinical and prevailing local features were analyzed. RESULTS: A total of 10709 patients were enrolled, including antral (42.97%), cardia (34.30%), and stomach body (18.41%) gastric cancer cases. Cancer in the cardia had the highest male:female ratio, proportion of elderly patients, and patients with complications, including hypertension, diabetes, cerebrovascular, and coronary diseases (P < 0.001). gastric cancer involving the antrum showed the lowest proportion of patients from rural areas and accounted for the highest hospitalization rate and cost (each P < 0.001). The proportion of patients with cancer involving the cardia increased with an increase in the number of gastroesophageal reflux disease cases during the same period (P < 0.001). Multivariate analysis revealed that tumor location in the cardia increased the risk of in-hospital mortality (P = 0.046). Anatomical subsite was not linked to postoperative complications. CONCLUSION: The features of gastric cancer based on the anatomical site differ between northern China and other regions, both globally and within the country. Social factors may account for these differences and should affect policy-making and clinical practice.

Combining single-cell sequencing data to construct a prognostic signature to predict survival, immune microenvironment, and immunotherapy response in gastric cancer patients.

Background and objective: Gastric cancer (GC) represents a major factor inducing global cancer-associated deaths, but specific biomarkers and therapeutic targets for GC are lacking at present. Therefore, the present work focused on developing an immune-related genetic signature at the single-cell level for categorizing GC cases and predicting patient prognostic outcome, immune status as well as treatment response. Methods: Single-cell RNA-sequencing (scRNA-seq) data were combined with bulk RNA-seq data in GC patients for subsequent analyses. Differences in overall survival (OS), genomic alterations, immune status, together with estimated immunotherapeutic outcomes were measured between different groups. Results: Nine cell types were identified by analyzing scRNA-seq data from GC patients, and marker genes of immune cells were also selected for subsequent analysis. In addition, an immune-related signature was established to predict OS while validating the prediction power for GC patients. Afterwards, a nomogram with high accuracy was constructed for improving our constructed signature's clinical utility. The low-risk group was featured by high tumor mutation burden (TMB), increased immune activation, and microsatellite instability-high (MSI-H), which were related to the prolonged OS and used in immunotherapy. By contrast, high-risk group was associated with microsatellite stability (MSS), low TMB and immunosuppression, which might be more suitable for targeted therapy. Meanwhile, the risk score generated by our signature was markedly related to the cancer stem cell (CSC) index. In addition, the immunotherapeutic response prediction accuracy of our signature was validated in an external dataset IMvigor210 cohort. Conclusion: A signature was constructed according to scRNA-seq data analysis. The signature-screened low- and high-risk patients had different prognoses, immune statuses and enriched functions and pathways. Such results shed more lights on immune status of GC, prognosis assessment, and development of efficient immunotherapeutic treatments.

Correlation Analysis between Airway Volume and Risk of Sleep Apnea/Periodontitis.

Objectives: Sleep apnea and periodontitis have high incidences in general population. They share common risk factors such as obesity, smoking, and aging. As cone-beam computed tomography becomes popular in dentistry, airway analysis is very accessible to dentists. However, not many studies have investigated the correlations between airway volume and risk of sleep apnea and periodontitis. The purpose of this retrospective study was to investigate the association between airway volume and the occurrence of sleep apnea and periodontitis. Material and Methods: Overall, 258 patients were enrolled (male: 118, female: 140, age from 13 to 88). axiUm® was used to collect demographical/physical information and the status of sleep apnea and periodontitis. Invivo™ software was utilized to measure airway dimensions. One-way ANOVA followed by Tukey's HSD post-hoc test and Pearson analysis were run to determine statistical difference in airway volumes among patients with various demographic and health status, and association of airway dimensions with their sleep apnea and periodontal conditions. Results: Sleep apnea patients had significantly higher body weight, body mass index, and significantly smaller airway compared to non-apnea patients (P < 0.05). Old age, male, and diabetes were found to be positively correlated with sleep apnea. No association between airway dimension and periodontal status was identified. Conclusions: Patients with high body mass index are at higher risk of developing constricted airway and sleep apnea. There appears to be no association between restricted airway and occurrence of periodontitis. Cone-beam computed tomography plays a critical role in identifying narrow airway and necessitating proper referral.

Application of deep machine learning for the radiographic diagnosis of periodontitis.

OBJECTIVE: Successful application of deep machine learning could reduce time-consuming and labor-intensive clinical work of calculating the amount of radiographic bone loss (RBL) in diagnosing and treatment planning for periodontitis. This study aimed to test the accuracy of RBL classification by machine learning. MATERIALS AND METHODS: A total of 236 patients with standardized full mouth radiographs were included. Each tooth from the periapical films was evaluated by three calibrated periodontists for categorization of RBL and radiographic defect morphology. Each image was pre-processed and augmented to ensure proper data balancing without data pollution, then a novel multitasking InceptionV3 model was applied. RESULTS: The model demonstrated an average accuracy of 0.87 ± 0.01 in the categorization of mild (< 15%) or severe (≥ 15%) bone loss with fivefold cross-validation. Sensitivity, specificity, positive predictive, and negative predictive values of the model were 0.86 ± 0.03, 0.88 ± 0.03, 0.88 ± 0.03, and 0.86 ± 0.02, respectively. CONCLUSIONS: Application of deep machine learning for the detection of alveolar bone loss yielded promising results in this study. Additional data would be beneficial to enhance model construction and enable better machine learning performance for clinical implementation. CLINICAL RELEVANCE: Higher accuracy of radiographic bone loss classification by machine learning can be achieved with more clinical data and proper model construction for valuable clinical application.

Effect of imatinib on oral wound healing after extraction: A rare case report.

BACKGROUND: Proper tissue repair and healing after oral surgery are vital to achieve optimal outcomes. Certain medications may interfere with wound healing, but this debilitating adverse drug reaction is often not reported in the literature. It is unknown whether imatinib (Gleevec; Novartis Pharmaceuticals) interferes with gingival healing after oral surgery. CASE DESCRIPTION: A 58-year-old man with a dislodged crown and core buildup of tooth no. 19 sought treatment at a prosthodontic clinic. After examination, the patient consented to extraction, ridge preservation, and future implant placement. He had previous surgical resection of a gastrointestinal stromal tumor and was taking 400 mg of imatinib daily. After extraction and ridge preservation, delayed soft-tissue healing and loss of the coronal portion of bone graft were observed at 8 weeks after surgery. Delayed wound healing was observed again after revision surgery. After imatinib therapy was paused, the adverse effect subsided and the wound healed properly. On the basis of causality assessment and clinical judgment, the authors determined that imatinib was the probable cause of this adverse drug reaction. To their best knowledge, this is the first report of delayed gingival healing after oral surgery secondary to imatinib. PRACTICAL IMPLICATIONS: Dental practitioners should consider the possibility of impaired healing among their patients taking imatinib, especially before procedures that damage gingival tissue, although this adverse drug reaction is not reported in the drug's package insert. Consult with the patient's oncologist is advised before dental manipulations; temporary discontinuation (or dose reductions) of imatinib may be warranted until wounded tissue heals properly.

Potential Microbiological Risk Factors Associated With Periodontitis and Periodontal Health Disparities.

Periodontitis disproportionately affects different racial and ethnic populations. In this study, we used qPCR to determine and compare oral microbial profiles in dental plaque samples from 191 periodontitis patients of different ethnic/racial backgrounds. We also obtained the periodontal parameters of these patients retrospectively using axiUm and performed statistical analysis using SAS 9.4. We found that in this patient cohort, neighborhood median incomes were significantly higher among Caucasians Americans (CAs) than among African Americans (AAs) and Hispanic Americans (HAs). Levels of total bacteria and Porphyromonas gingivalis, a keystone periodontal pathogen, were not evenly distributed among the three groups. We confirmed our previous findings that Streptococcus cristatus reduces P. gingivalis virulence potential and likely serves as a beneficial bacterium. We also showed the ratio of S. cristatus to P. gingivalis to be significantly higher in CAs than in HAs and AAs. Our results suggest that higher levels of P. gingivalis and lower ratios of S. cristatus to P. gingivalis may contribute to periodontal health disparities.

Ginsenoside distribution in different architectural components of Panax notoginseng inflorescence and infructescence.

The roots of Panax notoginseng (Burk) F. H. Chen are used as a highly valuable Chinese herbal medicine in the prevention and treatment of cardiovascular and hematological diseases. Several aerial parts of plant are usually abandoned as the wastes. Panax notoginseng inflorescence (IFO) is commonly used as a folk medicine and dietary ingredient, its fruiting stage is referred as infructescence (IFU). Owing to high chemical complexity and structural similarity of ginsenosides, the co-eluting phenomenon, especially for the isomers, is inevitable in the chromatogram, resulting in the inaccurate quantitation. A novel LCMS method using hybrid positive full scan and multiple reaction monitoring (MRM) modes was developed to characterize ginsenoside distribution in different architectural components of IFO and IFU. MRM was performed for the quantification of G-Ra2 and NG-Fp2, a pair of co-eluting isomers with identical negative MS and MS/MS characteristics, and full scan was conducted to quantify other investigated saponins. Our data indicate that flower buds have the highest abundance of the summed saponins, fruit pedicel and fruit pericarp, commonly considered as the useless by-products of seed processing, contain the abundant saponins. Additionally, the contents of the detected ginsenosides in these architectural components significantly increased along with their growth years. Our findings will facilitate comprehensive utilization and exploitation of P. notoginseng inflorescence and infructescence.

Application of three-dimensional proximal isovelocity surface area method in tricuspid regurgitation quantification.

OBJECTIVES: Recently, three-dimensional proximal isovelocity surface area (3D PISA) method has already been widely used in tricuspid regurgitation assessment. This study attempts to demonstrate the feasibility and accuracy of 3D PISA quantifying tricuspid regurgitation and explore the clinical value of 3D PISA in quantifying tricuspid regurgitation. METHODS: Fifty-four patients with more than mild tricuspid regurgitation (TR) were enrolled. Effective regurgitant orifice area (EROA) and regurgitant volume (Rvol) were assessed by transthoracic 3D PISA method and three-dimensional vena contracta area (3D VCA) method. The 3D VCA was used as reference method. We analyzed the correlation and differences of EROA between 3D PISA method and the reference method. RESULTS: Both EROA and Rvol assessed by the 3D PISA had good correlations with the reference method, particularly in the assessment of eccentric jets, with the correlation coefficients of r (EROA) = 0.83, P < 0.001, r (Rvol) = 0.90, P < 0.001, respectively. 3D PISA method had good agreement with 3D VCA method in grading TR. Intra-observer and inter-observer agreement were also good. CONCLUSIONS: Three-dimensional proximal isovelocity surface area method can accurately quantify the degree of tricuspid regurgitation with good repeatability and shorter time-consuming, which is worthy of further study. 3D PISA method is expected to be a new method for evaluating tricuspid regurgitation in clinic practice.

Frequency of Tongue Cleaning Impacts the Human Tongue Microbiome Composition and Enterosalivary Circulation of Nitrate.

The oral microbiome has the potential to provide an important symbiotic function in human blood pressure physiology by contributing to the generation of nitric oxide (NO), an essential cardiovascular signaling molecule. NO is produced by the human body via conversion of arginine to NO by endogenous nitric oxide synthase (eNOS) but eNOS activity varies by subject. Oral microbial communities are proposed to supplement host NO production by reducing dietary nitrate to nitrite via bacterial nitrate reductases. Unreduced dietary nitrate is delivered to the oral cavity in saliva, a physiological process termed the enterosalivary circulation of nitrate. Previous studies demonstrated that disruption of enterosalivary circulation via use of oral antiseptics resulted in increases in systolic blood pressure. These previous studies did not include detailed information on the oral health of enrolled subjects. Using 16S rRNA gene sequencing and analysis, we determined whether introduction of chlorhexidine antiseptic mouthwash for 1 week was associated with changes in tongue bacterial communities and resting systolic blood pressure in healthy normotensive individuals with documented oral hygiene behaviors and free of oral disease. Tongue cleaning frequency was a predictor of chlorhexidine-induced changes in systolic blood pressure and tongue microbiome composition. Twice-daily chlorhexidine usage was associated with a significant increase in systolic blood pressure after 1 week of use and recovery from use resulted in an enrichment in nitrate-reducing bacteria on the tongue. Individuals with relatively high levels of bacterial nitrite reductases had lower resting systolic blood pressure. These results further support the concept of a symbiotic oral microbiome contributing to human health via the enterosalivary nitrate-nitrite-NO pathway. These data suggest that management of the tongue microbiome by regular cleaning together with adequate dietary intake of nitrate provide an opportunity for the improvement of resting systolic blood pressure.

Comparison of periodontal evaluation by cone-beam computed tomography, and clinical and intraoral radiographic examinations.

OBJECTIVES: Cone-beam computed tomography (CBCT) has been widely used in many fields of dentistry. However, little is known about the accuracy of CBCT for evaluation of periodontal status. The objective of this study was to compare and correlate periodontal assessments among CBCT, clinical attachment loss (CAL) measurement, and periapical (PA)/bitewing (BW) radiography. METHODS: Eighty patients (28 males, 52 females; age range, 19-84 years) from the University of Texas School of Dentistry at Houston were evaluated retrospectively. Measurements were taken on the central incisors, canines, and first molars of the right maxilla and left mandible. CAL was extracted from periodontal charts. The radiographic distance from the cementum-enamel junction (CEJ) to the alveolar crest was measured for tooth mesial and distal sites on PA/BW and CBCT images using MiPacs software and Anatomage Invivo software, respectively. One-way ANOVA and Pearson analysis were performed for statistical analyses. RESULTS: The CEJ-crest distances for CBCT, PA/BW, and CAL were 2.56 ± 0.12, 2.04 ± 0.12, and 2.08 ± 0.17 mm (mean ± SD), respectively. CBCT exhibited larger values than the other two methods (p < 0.05). There were highly significant positive correlations among CBCT, PA/BW, and CAL measurements at all examined sites (p < 0.001). The Pearson correlation coefficient was higher for CBCT with CAL relative to PA/BW with CAL, but the difference was not significant (r = 0.64 and r = 0.55, respectively, p > 0.05). CONCLUSIONS: This study validates the suitability of CBCT for periodontal assessment. Further studies are necessary to optimize the measurement methodology with CBCT.

A retrospective study on molar furcation assessment via clinical detection, intraoral radiography and cone beam computed tomography.

BACKGROUND: Accurate determination of bone loss at the molar furcation region by clinical detection and intraoral radiograph is challenging in many instances. Cone beam computed tomography (CBCT) is expected to open a new horizon in periodontal assessment. The purpose of this study was to compare and correlate accuracy of molar furcation assessment via clinical detection, intraoral radiography and CBCT images. METHODS: Eighty-three patients with chronic periodontitis who had existing CBCT scans were included. Furcation involvement was assessed on maxillary and mandibular first molars. Periodontal charts (modified Glickman's classification), intraoral (periapical and/or bitewing) radiographs (recorded as presence or absence) and axial CBCT reconstructions were used to evaluate furcation involvement on buccal and palatal/lingual sites. The correlation of furcation assessment by the three methods was evaluated by Pearson analysis. RESULTS: There were significant correlations (p < 0.05) between clinical detection and intraoral radiography, clinical detection and CBCT, as well as intraoral radiography and CBCT at all the measured sites (r values range between 0.230 to 0.644). CBCT generally exhibited higher correlation with clinical detection relative to intraoral radiography, especially at distal palatal side of maxillary first molar (p < 0.05). In addition, CBCT provided more accurate assessment, with bone loss measurement up to 2 decimals in millimeters, whereas clinical detection had 3 classes and the intraoral radiographs usually only detected the presence of furcation involvement in Glickman Class 2 and 3. CONCLUSIONS: This study validates that CBCT is a valuable tool in molar furcation assessment in addition to clinical detection and intraoral radiography.

TGF-ß signaling regulates DACT1 expression in intestinal epithelial cells.

DACT1, was first identified as a Dishevelled-associated antagonist of Wnt signaling pathway. It has been reported that DACT1 functions in embryonic development and tumorigenesis. However, the regulation of DACT1 still remains unclear. We found Wnt signaling has no effect on DACT1, but TGF-ß increases expression of DACT1 in intestinal epithelial cells. In addition, the minimal promoter is located in the region of -500bp to +1bp and the region between -3000bp to +1bp enhanced promoter activity. Site-directed mutation analysis was performed and indicated that potential regulatory elements was near -335bp. Our study provided the basic information for the exploration of DACT1 regulation and expression. Moreover, TGF-ß inhibits Wnt signaling to enhance the function of DACT1 inhibiting Wnt signaling.

Cone Beam Computed Tomography of mandibular bone density in non-diabetic vs. diabetic populations.

BACKGROUND: The successful placement of dental implant largely depends on the properties of alveolar bone at the recipient site. Systemic conditions such as diabetes mellitus could impair bone quality and compromise implant treatment. However, limited information in this area exists so far. The objective of the study is to use cone beam computed tomography (CBCT) to assess mandibular bone mineral density (BMD) in diabetic and non-diabetic populations. METHODS: The patients who had CBCT scans in the school from 2011-2015 were screened, and 14 diabetic and 14 non- diabetic patients with matched age, gender, and ethnicity were recruited. BMD was measured on reconstructed CBCT sagittal views at 7 mm2 rectangular areas on 6 sites for each patient. For cortical bone, BMD was measured at the inferior border of mandible in the midline and between the first and second premolar bilaterally. For cancellous bone, BMD was measured in the midline of mandible halfway between the lingual foramen/canal and the inferior border of mandible, and at the premolar area halfway between the mandibular canal and the inferior border of mandible bilaterally. For diabetic patients, the glycosylated hemoglobin (HbAlc) values were obtained after informed consent. Statistical significant difference was set at p <0.05. The correlation between BMD and the age, gender, and HbAlc value of the patients was analyzed. An institutional IRB approval was obtained for the study. RESULTS: Diabetic patients had significantly lower cancellous BMD than non-diabetic subjects in the posterior mandibles (367 vs. 430, p<0.05). For both groups, cancellous BMD in the posterior mandible was significantly lower than that of anterior mandible. CONCLUSIONS: Diabetic patients have decreased BMD in the posterior mandible which could adversely affect implant placement at these areas.

Functional Advantages of Porphyromonas gingivalis Vesicles.

Porphyromonas gingivalis is a keystone pathogen of periodontitis. Outer membrane vesicles (OMVs) have been considered as both offense and defense components of this bacterium. Previous studies indicated that like their originating cells, P. gingivalis vesicles, are able to invade oral epithelial cells and gingival fibroblasts, in order to promote aggregation of some specific oral bacteria and to induce host immune responses. In the present study, we investigated the invasive efficiency of P. gingivalis OMVs and compared results with that of the originating cells. Results revealed that 70-90% of human primary oral epithelial cells, gingival fibroblasts, and human umbilical vein endothelial cells carried vesicles from P. gingivalis 33277 after being exposed to the vesicles for 1 h, while 20-50% of the host cells had internalized P. gingivalis cells. We also detected vesicle-associated DNA and RNA and a vesicle-mediated horizontal gene transfer in P. gingivalis strains, which represents a novel mechanism for gene transfer between P. gingivalis strains. Moreover, purified vesicles of P. gingivalis appear to have a negative impact on biofilm formation and the maintenance of Streptococcus gordonii. Our results suggest that vesicles are likely the best offence weapon of P. gingivalis for bacterial survival in the oral cavity and for induction of periodontitis.