Changes in composition and enamel demineralization inhibition activities of gallic acid at different pH values.

BACKGROUND: Gallic acid (GA) has been shown to inhibit demineralization and enhance remineralization of enamel; however, GA solution is highly acidic. This study was to investigate the stability of GA solutions at various pH and to examine the resultant effects on enamel demineralization. METHODS: The stability of GA in H2O or in phosphate buffer at pH 5.5, pH 7.0 and pH 10.0 was evaluated qualitatively by ultraviolet absorption spectra and quantified by high performance liquid chromatography with diode array detection (HPLC-DAD). Then, bovine enamel blocks were subjected to a pH-cycling regime of 12 cycles. Each cycle included 5 min applications with one of the following treatments: 1 g/L NaF (positive control), 4 g/L GA in H2O or buffered at pH 5.5, pH 7.0 and pH 10.0 and buffers without GA at the same pH (negative control), followed by a 60 min application with pH 5.0 acidic buffers and a 5 min application with neutral buffers. The acidic buffers were analysed for dissolved calcium. RESULTS: GA was stable in pure water and acidic condition, but was unstable in neutral and alkaline conditions, in which ultraviolet spectra changed and HPLC-DAD analysis revealed that most of the GA was degraded. All the GA groups significantly inhibited demineralization (p < 0.05) and there was no significant difference of the inhibition efficacy among different GA groups (p > 0.05). CONCLUSIONS: GA could inhibit enamel demineralization and the inhibition effect is not influenced by pH. GA could be a useful source as an anti-cariogenic agent for broad practical application.

Self-Assembled Nanoparticles from the Amphiphilic Prodrug of Resiquimod for Improved Cancer Immunotherapy.

Tumor-associated macrophages (TAMs) usually adopt a tumor-promoting M2-like phenotype, which largely impedes the immune response and therapeutic efficacy of solid tumors. Repolarizing TAMs from M2 to the antitumor M1 phenotype is crucial for reshaping the tumor immunosuppressive microenvironment (TIME). Herein, we developed self-assembled nanoparticles from the polymeric prodrug of resiquimod (R848) to reprogram the TIME for robust cancer immunotherapy. The polymeric prodrug was constructed by conjugating the R848 derivative to terminal amino groups of the linear dendritic polymer composed of linear poly(ethylene glycol) and lysine dendrimer. The amphiphilic prodrug self-assembled into nanoparticles (PLRS) of around 35 nm with a spherical morphology. PLRS nanoparticles could be internalized by antigen-presenting cells (APCs) in vitro and thus efficiently repolarized macrophages from M2 to M1 and facilitated the maturation of APCs. In addition, PLRS significantly inhibited tumor growth in the 4T1 orthotopic breast cancer model with much lower systemic side effects. Mechanistic studies suggested that PLRS significantly stimulated the TIME by repolarizing TAMs into the M1 phenotype and increased the infiltration of cytotoxic T cells into the tumor. This study provides an effective polymeric prodrug-based strategy to improve the therapeutic efficacy of R848 in cancer immunotherapy.

An Injectable Nanocomposite Hydrogel Improves Tumor Penetration and Cancer Treatment Efficacy.

Hydrogel as a local drug depot can increase drug concentration at the tumor site. However, conventional drug-loaded hydrogel is typically formed by direct dissolution of drug molecules inside the hydrogel, which usually suffers from limited drug retention and poor tumor penetration. In this study, a nanocomposite hydrogel consisting of oxaliplatin (OXA)-conjugated G5 polyamidoamine (G5-OXA) and oxidized dextran (Dex-CHO) is constructed to improve local drug delivery. The OXA-containing nanocomposite hydrogel (denoted as PDO gel) is injectable and could maintain in vivo up to more than three weeks, which increases drug retention in tumor tissues. More interestingly, G5-OXA released from the PDO gel show potent tumor penetration mainly through an active transcytosis process. In vivo antitumor studies in an orthotopic 4T1 tumor model show that PDO gel significantly inhibits primary tumor growth as well as the metastasis. In addition, the PDO gel can also activate the immunosuppressive tumor microenvironment through immunogenic cell death effect, and further improves therapeutic efficacy with the combination of PD-1 antibody. These results demonstrate that the nanocomposite hydrogel can simultaneously enhance the retention and penetration of chemotherapeutic drugs via the combination of both advantages of hydrogel and nanoparticles, which provides new insights for the design of local drug delivery systems. STATEMENT OF SIGNIFICANCE: Hydrogel represents an important class of local drug delivery depot. However, conventional drug-loaded hydrogel is usually achieved by direct dissolution of small drug molecules inside the hydrogel, which typically suffers from limited drug retention and poor tumor penetration. Herein, we developed a nanocomposite hydrogel, which could gradually degrade and release drug-conjugated small nanoparticles (∼ 6 nm) for improved tumor penetration through the combination of an active transcytosis process and a passive diffusion process. This nanocomposite hydrogel system improved tumor penetration and retention of drug in primary tumors as well as the drug deposition in lymph nodes, which significantly suppressed tumor growth and metastasis.

Risk indicators for root caries in older adults using long-term social care facilities in Hong Kong.

OBJECTIVE: To investigate risk indicators associated with root caries among the Hong Kong older adults who attended long-term care facilities regularly. METHODS: Nonfrail older adults with at least six natural teeth from 10 long-term social or residential care facilities were examined. The clinical examinations were conducted by two calibrated dentists in the institutions. Portal dental chairs, intra-oral LED lights, disposable mouth mirrors, periodontal probes and CPI probes were used in the examinations. Negative binomial regression analyses were performed to identify the risk indicators associated with root caries. Multilevel logistic regression analyses were conducted to detect the associations between DF-root and D-root, and selected person-level and tooth surface-level factors. RESULTS: A total of 353 older adults (mean age 74.9 years) were examined. The prevalence of DF-root and D-root was 43.1% and 30.0%, respectively. The mean DF-root and D-root scores were 1.3 and 0.7, respectively. Relative to participants without DF-root, those with root caries experience were older and had more exposed root surfaces, and a higher proportion were partial denture wearers. There was a positive correlation between the DF-root score and the age of the participant, and with the numbers of exposed root surfaces, missing teeth and teeth with coronal caries. Higher prevalence of DF-root was observed among the older participants, and caries experience of root surfaces with greater gingival recession and visible plaque was higher. Lingual root surfaces and roots in the mandibular anterior region had the lowest rates of DF-root. CONCLUSIONS: People who are older have a higher prevalence and severity of root caries. Coronal caries experience, maxillary teeth, buccal root surfaces, gingival recession and plaque on the root surface are positively associated with root caries in older adults.

Risk predictors of dental root caries: A systematic review.

OBJECTIVES: To identify the risk predictors of root caries and to describe their relationship with the incidence and increment of root caries. DATA: Observational longitudinal studies. SOURCES: Four electronic databases (PubMed, MEDLINE, EMBASE, and Scopus) (From 1 January 1990 to 31 January 2019). STUDY SELECTION: Information on the factors associated with the incidence or increment of decayed and filled root surfaces (DF-root) and/or decayed root surfaces (D-root) were extracted by two reviewers independently. The factors were put into six categories, namely social-demographic background, general health, health behaviors, fluoride exposure, oral health habits and oral health condition. From the 440 potential papers identified, 19 papers reporting on 16 cohort studies were finally included. The total sample size was 7340 participants from different countries worldwide, with age ranging from 20 to 100 years. Positive correlations between new root caries and age, baseline root caries experience, gingival recession and use of tobacco were reported while negative correlations were found for socio-economic status, good oral hygiene and use of fluorides. Mixed findings were detected for the association between new root caries and the number of natural teeth. CONCLUSION: This systematic review discovered a number of root caries risk predictors in different categories. People who are older, in lower socio-economic status or tobacco users, and those with more root caries experience, gingival recession and poor oral hygiene have higher risk of developing new root caries. CLINICAL SIGNIFICANCE: This systematic review provides support that improvement of oral hygiene, prevention of gingival recession, and use of fluoride would be useful strategy for prevention of new root caries.

Effectiveness of professional fluorides against enamel white spot lesions during fixed orthodontic treatment: A systematic review and meta-analysis.

OBJECTIVES: To systematically review the effectiveness of professionally applied topical fluorides in the prevention and reversal of Enamel White Spot Lesions (EWSLs) occurring during multi-bracketed fixed orthodontic treatment. DATA: Randomized/quasi-randomized controlled clinical trials. SOURCES: Four electronic databases and grey literature (up to February, 2018). STUDY SELECTION: Two reviewers independently selected studies, extracted data and assessed risk of bias using the Cochrane Risk of bias tool 2.0. Only 11 studies fulfilled the inclusion criteria, seven assessing reversal and four assessing prevention of EWSLs. Six of the eleven studies were included for quantitative synthesis, three assessing prevention and three assessing reversal of EWSLs. CONCLUSIONS: Using the Mantel-Haenszel fixed-effect method, the risk ratio was found to be 0.39 (95% C.I.: 0.26-0.59) in studies evaluating the prevention of EWSLs. On employing an inverse-variance fixed-effect method for mean DIAGNOdent scores, the standardized mean difference was found to be 0.57 less in the professional topical fluoride group than the control group (95% C.I.: 0.23 to -0.91) in studies evaluating reversal of EWSLs. Professional topical fluoride application brought 25-30% reduction in the incidence of EWSLs after debonding; however, the effect of professional topical fluoride application in a reversal of EWSLs was unclear due to the concerns in interpreting DIAGNOdent values to estimate EWSLs. CLINICAL SIGNIFICANCE: Due to a limited number of clinical trials, further research is warranted to identify the type of professional fluoride agent, the concentration of fluoride and the frequency of applications in prevention or reversal of EWSLs in patients undergoing multi-bracketed fixed orthodontic treatment.

[Three-year retrospective clinical evaluation of pulp-less molars with defects of varying degree repaired by cast ceramic onlays of three marginal types].

OBJECTIVE: This study aimed to evaluate the clinical effect of pulp-less molars with defects of different degrees repaired by cast ceramic onlays of three marginal types. METHODS: A total of 165 endodontically treated molars of 105 patients were included in this study and were divided into three kinds of defect (mild, moderate, severe) according to the number of remaining axial walls. Each defect was divided into three groups according to the shape of edge to edge, bevel edge, and concave shoulder. After tooth preparation, the casting of ceramic onlays was performed. Treatment follow-up was done for the evaluation of the success and survival rates of three groups under the same defect. RESULTS: The average follow-up was 925.44 days. Under the mild defect, the success and survival rates of the edge to edge onlays were respectively 100% and 100%; bevel edge onlays, 100% and 100%; and concave shoulder onlays, 94.4% and 100%. Under the moderate defect, the success and survival rates of the edge to edge onlays were respectively 96.0% and 100%; bevel edge onlays, 80.0% and 93.3%; and concave shoulder onlays, 95.2% and 95.2%. Under the severe defect, the success and survival rates of the edge to edge onlays were respectively 95.2% and 100%; bevel edge onlays, 73.7% and 89.5%; and concave shoulder onlays, 73.3% and 80.0%. Under different defects, the success or survival rates of the three kinds of onlays had no significant difference (P>0.05). CONCLUSIONS: The edge to edge type is the most preferable way of onlay tooth preparation and can achieve good clinical results in the mild, middle, and severe tooth defection with root canal treatment.

Radiation caries in nasopharyngeal carcinoma patients after intensity-modulated radiation therapy: A cross-sectional study.

BACKGROUND/PURPOSE: The exact dose of intensity-modulated radiation therapy (IMRT) associated with tooth damage is mostly unknown. We aim to evaluate the severity of dental lesions after IMRT and the correlation with the radiation dose to the dentition in patients with nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS: This was a cross-sectional study of 42 patients with NPC who completed IMRT in 2011. Each premolar tooth was divided into 13 sites. Teeth were evaluated using a validated index and subsequently categorized at each divided site. The relationship between dose distribution and the caries severity score was analyzed using logistic models. The odds of developing caries damage were evaluated using odds ratios. RESULTS: A total of 4342 sites from 334 premolar teeth were evaluated. For sites exposed to 30-60 Gy, the odds of developing caries damage were 12-200 times greater compared with sites unexposed to IMRT. A new radiation caries lesion was likely to occur when the dose was >35.8 Gy after 17 days' radiation therapy (P < 0.05). CONCLUSION: The findings suggest that new tooth damage was likely to occur at doses > 35.8 Gy, and care should be taken throughout the treatment planning process to limit tooth doses to < 50 Gy in NPC patients.

Investigation of salivary function and oral microbiota of radiation caries-free people with nasopharyngeal carcinoma.

Radiation caries have been reported to be correlated with radiotherapy-induced destruction of salivary function and changes in oral microbiota. There have been no published reports detailing patients who have remained radiation caries-free following radiotherapy for nasopharyngeal carcinoma. The aim of this study was to investigate the relationship between salivary function, oral microbiota and the absence of radiation caries. Twelve radiation caries-free patients and nine patients exhibiting radiation caries following irradiated nasopharyngeal carcinoma were selected. V40, the dose at which the volume of the contralateral parotid gland receives more than 40 Gy, was recorded. Stimulated saliva flow rate, pH values and buffering capacity were examined to assess salivary function. Stimulated saliva was used for molecular profiling by Denaturing Gradient Gel Electrophoresis. Mutans streptococci and Lactobacilli in saliva were also cultivated. There were no significant differences in V40 between radiation caries-free individuals and those with radiation caries. Compared with normal values, the radiation caries-free group had significantly decreased simulated saliva flow rate, while there were no significant differences in the saliva pH value and buffering capacity. Similar results were observed in the radiation caries group. There was no statistical difference in microbial diversity, composition and log CFU counts in cultivation from the radiation caries-free group and the radiation caries group. Eleven genera were detected in these two groups, among which Streptococcus spp. and Neisseria spp. had the highest distribution. Our results suggest that changes in salivary function and in salivary microbiota do not explain the absence of radiation caries in radiation caries-free individuals.