An experiential service-learning project on oral health examination and education.

BACKGROUND: It has been demonstrated that experiential service-learning is effective in fields including public health and medicine. Preventive Dentistry is a practical course, and Oral Health Examination and Education is a topic that is suitable for teaching with experiential service-learning. This study describes an example of experiential service-learning in Preventive Dentistry named "Oral Health Examination and Education Project" and also evaluates its effectiveness among dental students. METHODS: A total of 108 dental students in their fourth year participated in this project in 2022. The project was composed of six sections: theoretical teaching, field investigation, data collection and analysis, investigation report writing and creating oral health education materials, oral health education and students' evaluation of the project. RESULTS: During this project, students learned how to perform surveys related to oral health, wrote an investigation report, created oral health education materials, and provided oral health education for children. Students were demonstrated an improvement in their academic performance for theoretical knowledge related to Oral Health Examination and Education in comparison with the students in the previous year. Over 90% of students expressed their preference for the learning method of experiential service and believed that it helped them to better understand the course material. They also recommended this teaching method for future classes. CONCLUSIONS: This study indicated that an experiential service-learning approach within this scope was highly beneficial to students because it provided them with the opportunity to understand the practical application of their coursework and obtain valuable experience in the field. This research suggests that oral epidemiology instructors in dental and oral public health programs should pay more attention to incorporate similar experiential projects into their curriculum with the aim of better preparing students for careers in oral public health.

The rs35874116 single nucleotide polymorphism increases sweet intake and the risk of severe early childhood caries: a case-control study.

BACKGROUND: Dental caries is one of the most prevalent chronic diseases worldwide among children. The rs35874116 single nucleotide polymorphism (SNP) in the sweet receptor gene TAS1R2 has been associated with dental caries at a high risk in permanent teeth among school children and adults. To date, little is known about the association of this SNP with sweet intake and caries risk in the primary school children. METHODS: Total of 236 children were included, namely 118 subjects in the non-caries (NC) group and severe early childhood caries (S-ECC) group, respectively. Oral mucosa cells were collected from all the selected children, and the full length of exon 3 in TAS1R2 was sequenced to analyse rs35874116 polymorphism. A questionnaire was used to collect information about socio-demographic information, frequency of sweet intake and oral hygiene habits. Multiple logistic regression models were applied to assess the relationship of rs35874116 polymorphism with frequency of sweet intake and S-ECC among the five-year-old children. RESULTS: Children with the TT genotype of rs35874116 had a higher frequency of sweet intake than CT/CC carriers (51.3% vs. 32.7%; x2 = 5.436, p = 0.020), and S-ECC individuals were more likely to be TT genotype carriers than NC individuals (53.5% vs. 46.5%; x2 = 4.353, p = 0.037). Multiple logistic regression analyses showed that the TT genotype of rs35874116 was not only significantly related to the frequency of sweet intake (OR = 2.25, 95% CI = 1.14-4.44) but also significantly associated with S-ECC (OR = 2.11, 95% CI = 1.01 ~ 4.42). CONCLUSIONS: The rs35874116 polymorphism might increase sweet intake and the risk of S-ECC among five-year-old children in Nanning, China.

A novel three-dimensional morphological analysis of idiopathic condylar resorption following stabilisation splint treatment.

Bone modelling evaluation is important for monitoring idiopathic condylar resorption (ICR) progress. To compare condylar modelling in ICR patients treated with or without stabilisation splints (SSs). Eighty-four condyles from 84 ICR patients were studied: 42 received SS therapy (SS group); 42 received conventional therapy (control group). Cone-beam computed tomography images at diagnosis (T0) and after at least 6 months (T1) were used for three-dimensional reconstruction. Volume differences between T0 and T1 (δV) were used to evaluate the amount of modelling. Percentage of growth area (PCT) was used to assess the condylar surface growth tendency. No significant change in condylar volume was found in the SS group, whereas that in the control group was significantly decreased at T1 (P <.0001). The amount of modelling differed among condylar subregions within the SS group: among 6 subregions (P =.0137), between anterior and posterior regions (P =.0336) and between lateral, intermediate and medial regions (P =.0275). Control group condylar subregions showed no significant differences in the amount of modelling. The anabolic modelling tendency of the total condylar surface in the SS group was greater than that in the control group (P =.0251); however, there were no statistical differences in PCTs among condylar subregions in either group. SS therapy effectively reduced further bone destruction and promoted condylar modelling. Three-dimensional morphological analysis is a novel method that can accurately evaluate the amount of bone modelling and growth tendency in ICR patients.

A two-week single-group longitudinal test of a new sonic-powered toothbrush simulating the 'bass brushing technique' with tapered bristles on the brush head for reduction of dental plaque and gingivitis.

OBJECTIVE: To investigate the effect of a new powered toothbrush with tapered bristles on the brush head for the reduction of dental plaque and gingivitis. METHODS: This was a single-centre, single-group, longitudinal clinical trial. Thirty-two participants who were typical manual toothbrush users were recruited and assigned the sonic-powered brush. Interviews were arranged on the 1st , 4th , and 15th days which represented the baseline (T1 ), middle (T2 ) and final (T3 ) time points, respectively. At each visit, the plaque index (PlI), gingival index (GI), bleeding on probing (BOP) and probing depth (PD) were recorded for the Ramfjord index teeth, gingival crevicular fluid(GCF) samples were collected and the proportions of eight periodontal pathogenic bacteria were analysed. Repeated-measures analysis of variance (ANOVA) was used for comparisons at different time points. RESULTS: PlI was significantly reduced by 41.67% from T1 to T2 (p<0.001) and decreased by 18.57% from T2 to T3 (p=0.003). GI also varied significantly from T1 to T2 (p=0.018) and T1 to T3 (p=0.037). A 35.86% reduction in the BOP percentage occurred after using the sonic-powered toothbrush for 3 days (p=0.001). However, no significant difference was observed in the mean values of PD at different examination intervals (p=0.529). There was no significant difference in the proportions of bacteria between T1 and T3 (p>0.05). CONCLUSION: This research demonstrated the efficacy of the sonic-powered brush handle together with tapered bristles on the brush in reducing plaque and gingivitis within a short time period.

Genetic polymorphism of scrA gene of Streptococcus mutans isolates is not associated with biofilm formation in severe early childhood caries.

BACKGROUND: To explore and analyse the association between biofilm and the genetic polymorphisms of scrA gene of EnzymeIIscr found in clinical isolates of Streptococcus mutans (S. mutans) from severe early childhood caries (S-ECC) in 3 years old children. METHODS: Clinical strains of S. mutans were conserved from a previous study. Thirty strains of S. mutans from the S-ECC group and 30 strains of S. mutans from the caries free (CF) group were selected. Biomass and viability of biofilm formed by the strains were evaluated by crystal violet and alamar blue assay. Genomic DNA was extracted from the S. mutans isolates. PCR was conducted to amplify scrA gene. After purified and sequenced the PCR products, BioEdit sofeware was used to analyse the sequence results. A chi-square test was used to compare the results. RESULTS: Compared to the CF group, the biomass of S-ECC group was higher (P = 0.0424). However, the viability of the two groups showed no significant difference. All 60 clinically isolated S. mutans strains had a 1995 base pair (bp) scrA gene. Forty-nine point mutations were identified in scrA from the 60 clinical isolates. There were 17 missense point mutations at the 10, 65, 103, 284, 289, 925, 1444, 1487, 1494, 1508, 1553, 1576, 1786, 1822, 1863, 1886, and 1925 bp positions. The other 32 mutations were silent point mutations. No positions were found at active sites of ScrA. The statistic analyse showed no significant missense mutation rates between the two groups. CONCLUSIONS: There was no association between biofilm and genetic polymorphisms of scrA from S. mutans with S-ECC in 3 years old children.

Analysis of Small RNAs in Streptococcus mutans under Acid Stress-A New Insight for Caries Research.

Streptococcus mutans (S. mutans) is the major clinical pathogen responsible for dental caries. Its acid tolerance has been identified as a significant virulence factor for its survival and cariogenicity in acidic conditions. Small RNAs (sRNAs) are recognized as key regulators of virulence and stress adaptation. Here, we constructed three libraries of sRNAs with small size exposed to acidic conditions for the first time, followed by verification using qRT-PCR. The levels of two sRNAs and target genes predicted to be bioinformatically related to acid tolerance were further evaluated under different acid stress conditions (pH 7.5, 6.5, 5.5, and 4.5) at three time points (0.5, 1, and 2 h). Meanwhile, bacterial growth characteristics and vitality were assessed. We obtained 1879 sRNAs with read counts of at least 100. One hundred and ten sRNAs were perfectly mapped to reported msRNAs in S. mutans. Ten out of 18 sRNAs were validated by qRT-PCR. The survival of bacteria declined as the acid was increased from pH 7.5 to 4.5 at each time point. The bacteria can proliferate under each pH except pH 4.5 with time. The levels of sRNAs gradually decreased from pH 7.5 to 5.5, and slightly increased in pH 4.5; however, the expression levels of target mRNAs were up-regulated in acidic conditions than in pH 7.5. These results indicate that some sRNAs are specially induced at acid stress conditions, involving acid adaptation, and provide a new insight into exploring the complex acid tolerance for S. mutans.

Superior antimetastatic effect of pemetrexed-loaded gelatinase-responsive nanoparticles in a mouse metastasis model.

Novel pemetrexed-loaded gelatinase-responsive nanoparticles were prepared as a targeted delivery system to determine its potential for clinical therapy of malignant melanoma. The pemetrexed-loaded poly(ethylene glycol)(PEG)-peptide-poly(ε-caprolactone) (PCL) nanoparticles included a gelatinase-cleavage peptide and a PEG-PCL-based structure. The pemetrexed-loaded PEG-peptide-PCL nanoparticles have shown the best antimetastatic effect in experimental lung metastasis models. The expressions of CD133 and thymidylate synthetase of metastatic tumors were also evaluated in our studies. Our results showed that pemetrexed-loaded gelatinase-responsive nanoparticles may represent a potent drug delivery system for inhibiting pulmonary metastasis and our preclinical results can provide new avenues for clinical therapy of malignant melanoma.

iRGD Co-Administration with Paclitaxel-Loaded PLGA Nanoparticles Enhance Targeting and Antitumor Effect in Colorectal Cancer Treatment.

OBJECTIVE: To explore the targeting effect of PLGA-NP and iRGD co-administration with PTXPLGA NP (PTX-PLGA + iRGD) on colorectal cancer. METHODS: Whether PLGA-NP co-administration with iRGD peptide could show effective tumor-targeting ability in contrast to with PLGA-NP in colorectal cancer mice models was evaluated. Moreover, the chemotherapeutics Paclitaxel (PTX) was loaded into the PLGA-NP to impart anti-tumor efficiency to the PTX-PLGA. Whether iRGD co-administration with PTX-PLGA NP (PTX-PLGA + iRGD) in colorectal cancer models enabled PTX to achieve better anti-tumor efficiency and biocompatibility was further assessed. RESULTS: The targeting ability of PLGA-NP was enhanced in cell experiment and colorectal cancer mice models by co-administration of iRGD. As a result, PTX-PLGA + iRGD achieved better anti-tumor efficacy than PTX and PTX-PLGA. Conlusion: The nanocarrier based on PLGA with specific targeting ability could promote the clinical application of various chemotherapeutics similar to PTX. The combination of drug-loaded nanoparticles and iRGD could develop into a promising drug delivery system.

Combined delivery of salinomycin and docetaxel by dual-targeting gelatinase nanoparticles effectively inhibits cervical cancer cells and cancer stem cells.

Intra-tumor heterogeneity is widely accepted as one of the key factors, which hinders cancer patients from achieving full recovery. Especially, cancer stem cells (CSCs) may exhibit self-renewal capacity, which makes it harder for complete elimination of tumor. Therefore, simultaneously inhibiting CSCs and non-CSCs in tumors becomes a promising strategy to obtain sustainable anticancer efficacy. Salinomycin (Sal) was reported to be critical to inhibit CSCs. However, the poor bioavailability and catastrophic side effects brought about limitations to clinical practice. To solve this problem, we previously constructed gelatinase-stimuli nanoparticles composed of nontoxic, biocompatible polyethylene glycol-polycaprolactone (PEG-PCL) copolymer with a gelatinase-cleavable peptide Pro-Val-Gly-Leu-Iso-Gly (PVGLIG) inserted between the two blocks of the copolymer. By applying our "smart" gelatinase-responsive nanoparticles for Sal delivery, we have demonstrated specific accumulation in tumor, anti-CSCs ability and reduced toxicity of Sal-NPs in our previous study. In the present study, we synthesized Sal-Docetaxel-loaded gelatinase-stimuli nanoparticles (Sal-Doc NP) and confirmed single emulsion as the optimal method of producing Sal-Doc NPs (Sal-Doc SE-NP) in comparison with nanoprecipitation. Sal-Doc SE-NPs inhibited both CSCs and non-CSCs in mice transplanted with cervical cancer, and might be associated with enhanced restriction of epithelial-mesenchymal transition (EMT) pathway. Besides, the tumorigenic capacity and growing speed were obviously suppressed in Sal-Doc-SE-NPs-treated group in rechallenge experiment. Our results suggest that Sal-Doc-loaded gelatinase-stimuli nanoparticles could be a promising strategy to enhance antitumor efficacy and reduce side effects by simultaneously suppressing CSCs and non-CSCs.

Enamel and Dentin Caries Risk Factors of Adolescents in the Context of the International Caries Detection and Assessment System (ICDAS): A Longitudinal Study.

Objective: The objective of this study was to identify risk factors for enamel and dentin caries in adolescents. Method: This 1-year longitudinal study was conducted in 2018 and 2019; 13- to 14-year-old adolescents were recruited. The merged International Caries Detection and Assessment System (ICDAS) was used to identify caries. The relationships between the caries increment and variables were analyzed with a zero-inflated negative binomial (ZINB) regression model. Results: A total of 1,016 participants completed the assessment. The ZINB analysis found that individuals with caries at baseline were more likely to develop new dentin caries. Females, or individuals who had a high cariostat score had an increased likelihood of having a high ΔD4-6MFT score. Among the caries-free adolescents at baseline, females, or individuals who consumed snacks once or more than once a day were more likely to develop caries. Individuals from one-child families, who used fluoride toothpaste, and who had a high saliva buffering capability (pH≥4.25) had an increased likelihood of a low ΔD1-6MFT score. Conclusion: The results suggest that there are some specific risk factors of initiating of enamel caries in adolescents, including the frequency of snack consumption, sex, saliva buffering capability, fluoride toothpaste usage and belonging to a one-child family. In all adolescents, most of whom have enamel caries, the dentin caries risk factors were past caries experience, cariostat score and sex.

Prominent Enhancement of Cisplatin Efficacy with Optimized Methoxy Poly(ethylene glycol)-Polycaprolactone Block Copolymeric Nanoparticles.

Chemotherapy has been one of the major standard treatments for a variety of cancers. cis-Dichlorodiamminoplatiunum (II) (cisplatin, CDDP), as one of the anticancer agents, demonstrated excellent efficacy against tumor and has been an indispensable component in chemotherapy, chemoradiation, chemo-molecular targeted therapy and chemo-immunotherapy. However, its therapeutic concentration was limited since its inevitable toxicity. Previously, we have constructed CDDPloaded nanoparticles (NPs) with mixture of poly(ethyleneglycol)-polycaprolactone (PEG-PCL) and polycarprolactone (HOPCL) by a facile method. The most optimal proportion of the two copolymers was selected through a series of physical, chemical, cytological and histological evaluations. In the present study, we explored the mechanisms of NPs and observed the in vivo antitumor effect after administrating CDDP-loaded PEG-PCL NPs. Positron emission tomography as well as computed tomography (PET/CT) were adopted for detecting tumoral metabolic activity. Images from fluorescence microscope revealed superior cellular uptake of CDDP-loaded NPs with rhodamine B aggregated intracellularly in cancer cells. Similar apoptotic rates between free CDDP group and CDDP-loaded NPs group was measured by flow cytometry. Tumor volumes and murine weights confirmed the superiority of CDDP-loaded NPs in therapeutic efficacy as compared with free CDDP. Blood tests showed milder side effects in CDDP-loaded nanoparticle group. PET/CT images illustrated less uptake intensity of FDG in mice received CDDP-loaded NPs than free CDDP. Our results suggest that PEG-PCL/PCL NPs could be a promising antitumor drug carrier for CDDP delivery with solid efficacy and minor side effects.

Enhanced and Prolonged Antitumor Effect of Salinomycin-Loaded Gelatinase-Responsive Nanoparticles via Targeted Drug Delivery and Inhibition of Cervical Cancer Stem Cells.

BACKGROUND: Cervical cancer stem cells (CCSCs) represent a subpopulation of tumor cells that possess self-renewal capacity and numerous intrinsic mechanisms of resistance to conventional chemotherapy and radiotherapy. These cells play a crucial role in relapse and metastasis of cervical cancer. Therefore, eradication of CCSCs is the primary objective in cervical cancer therapy. Salinomycin (Sal) is an agent used for the elimination of cancer stem cells (CSCs); however, the occurrence of several side effects hinders its application. Nanoscale drug-delivery systems offer great promise for the diagnosis and treatment of tumors. These systems can be used to reduce the side effects of Sal and improve clinical benefit. METHODS: Sal-loaded polyethylene glycol-peptide-polycaprolactone nanoparticles (Sal NPs) were fabricated under mild and non-toxic conditions. The real-time biodistribution of Sal NPs was investigated through non-invasive near-infrared fluorescent imaging. The efficacy of tumor growth inhibition by Sal NPs was evaluated using tumor xenografts in nude mice. Flow cytometry, immunohistochemistry, and Western blotting were used to detect the apoptosis of CSCs after treatment with Sal NPs. Immunohistochemistry and Western blotting were used to examine epithelial-mesenchymal transition (epithelial interstitial transformation) signal-related molecules. RESULTS: Sal NPs exhibited antitumor efficacy against cervical cancers by inducing apoptosis of CCSCs and inhibiting the epithelial-mesenchymal transition pathway. Besides, tumor pieces resected from Sal NP-treated mice showed decreased reseeding ability and growth speed, further demonstrating the significant inhibitory ability of Sal NPs against CSCs. Moreover, owing to targeted delivery based on the gelatinase-responsive strategy, Sal NPs was more effective and tolerable than free Sal. CONCLUSION: To the best of our knowledge, this is the first study to show that CCSC-targeted Sal NPs provide a potential approach to selectively target and efficiently eradicate CCSCs. This renders them a promising strategy to improve the therapeutic effect against cervical cancer.

Antitumor Activity of Thermosensitive Hydrogels Packaging Gambogic Acid Nanoparticles and Tumor-Penetrating Peptide iRGD Against Gastric Cancer.

INTRODUCTION: Gambogic acid (GA) is proved to have anti-tumor effects on gastric cancer. Due to poor solubility, non-specific biological distribution, toxicity to normal tissues and short half-life, it is hard to be applied into the clinic. To overcome these issues, we developed a thermosensitive and injectable hydrogel composed of hydroxypropyl cellulose, silk fibroin and glycerol, with short gelling time, good compatibility and sustained release, and demonstrated that the hydrogel packaged with gambogic acid nanoparticles (GA-NPs) and tumor-penetrating peptide iRGD could improve the anti-tumor activity. METHODS: The Gelling time and micropore size of the hydrogels were regulated through different concentrations of glycerol. Controlled release characteristics of the hydrogels were evaluated with a real-time near-infrared fluorescence imaging system. Location of nanoparticles from different carriers was traced by confocal laser scanning microscopy. The in vivo antitumor activity of the hydrogels packaging GA-NPs and iRGD was evaluated by investigating tumor volume and tumor size. RESULTS: The thermo-sensitive properties of hydrogels were characterized by 3-4 min, 37°C, when glycerol concentration was 20%. The hydrogels physically packaged with GA-NPs and iRGD showed higher fluorescence intensity than other groups. The in vivo study indicated that the co-administration of GA-NPs and iRGD by hydrogels had higher antitumor activity than the GA-loaded hydrogels and free GA combining with iRGD. Free GA group showed few antitumor effects. Compared with the control group, the body weight in other groups had no obvious change, and the count of leukocytes and hemoglobin was slightly decreased. DISCUSSION: The hydrogel constructed iRGD and GA-NPs exerted an effective anti-tumor effect possibly due to retention effect, local administration and continuous sustained release of iRGD promoting the penetration of nanoparticles into a deep part of tumors. The delivery system showed little systemic toxicity and would provide a promising strategy to improve anti-gastric cancer efficacy.

Anti-EGFR-iRGD recombinant protein modified biomimetic nanoparticles loaded with gambogic acid to enhance targeting and antitumor ability in colorectal cancer treatment.

BACKGROUND: Red blood cell membrane-coated nanoparticle (RBCm-NP) platform, which consist of natural RBCm and synthetic polymeric core, can extend circulation time in vivo with an improved biocompatibility and stability of this biomimetic nanocarrier. To achieve better bioavailability of antitumor drugs that were loaded in RBCm-NPs, the functionalization of coated RBCm with specific targeting ability is essential. Bispecific recombinant protein anti-EGFR-iRGD, containing both tumor penetrating peptide (internalizing RGD peptide) and EGFR single-domain antibody (sdAb), seems to be an optimal targeting ligand for RBCm-NPs in the treatment of multiple tumors, especially colorectal cancer with high EGFR expression. MATERIALS AND METHODS: We modified the anti-EGFR-iRGD recombinant protein on the surface of RBCm-NPs by lipid insertion method to construct iE-RBCm-PLGA NPs and confirmed the presentation of active tumor-targeting ability in colorectal cancer models with high EGFR expression when compared with RBCm-PLGA NPs. In addition, potential anti-tumor drug gambogic acid (GA) was loaded into the NPs to endow the antitumor efficiency of iE-RBCm-GA/PLGA NPs. It was simultaneously evaluated whether GA can reach better biocompatibility benefiting from the improved antitumor efficiency of iE-RBCm-GA/PLGA NPs in colorectal cancer models. RESULTS: We successfully modified anti-EGFR-iRGD proteins on the surface of biomimetic NPs with integrated and stable "shell-core" structure. iE-RBCm-PLGA NPs showed its improved targeting ability in vitro (multicellular spheroids [MCS]) and in vivo (nude mice bearing tumors). Besides, no matter on short-term cell apoptosis at tumor site (terminal deoxyribonucleotidyl transferase-mediated dUTP nick end labeling [TUNEL]) and long-term tumor inhibition, iE-RBCm-GA/PLGA NPs achieved better antitumor efficacy than free GA in spite of the similar effects of cytotoxicity and apoptosis to GA in vitro. CONCLUSION: We expect that the bispecific biomimetic nanocarrier can extend the clinical application of many other potential antitumor drugs similar to GA and become a novel drug carrier in the colorectal cancer treatment.

Lipid insertion enables targeted functionalization of paclitaxel-loaded erythrocyte membrane nanosystem by tumor-penetrating bispecific recombinant protein.

BACKGROUND: There is currently much interest in cancer cell targeting and tumor penetrating for research and therapeutic purposes. PURPOSE: To improve targeting delivery of antitumor drugs to gastric cancer, in this study, a tumor-targeting biocompatible drug delivery system derived from erythrocyte membrane for delivering paclitaxel (PTX) was constructed. METHODS: Erythrocyte membrane of human red blood cells (RBCs) were used for preparing of erythrocyte membrane-derived vesicles. 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-(maleimide[polyethylene glycol]-3400) (DSPE-PEG-MAL), a phospholipid derivative, was used to insert tumor-targeting molecular into erythrocyte membrane-derived vesicles. A lipid insertion method was used to functionalize these vesicles without the need for direct chemical conjugation. Furthermore, a tumor-penetrating bispecific recombinant protein named anti-EGFR-iRGD was used for the first time in this work to enable nanosystem to target and penetrate efficiently into the tumor site. RESULTS: Paclitaxel (PTX)-loaded anti-EGFR-iRGD-modified erythrocyte membrane nano-system (anti-EGFR-iRGD-RBCm-PTX, abbreviated to PRP) were manufactured. PRP was spheroid, uniformly size, about 171.7±4.7 nm in average, could be stable in vitro for 8 days, and released PTX in a biphasic pattern. PRP showed comparable cytotoxicity toward human gastric cancer cells in vitro. In vivo studies showed that, PRP accumulated in tumor site within 2 h of administration, lasted longer than 48 h, and the tumor volume was reduced 61% by PRP treatment in Balb/c nude mice, without causing severe side effects. CONCLUSION: PRP has potential applications in cancer treatment and as an adjunct for other anticancer strategies.

Variation in Enamel Formation Genes Influences Enamel Demineralization In Vitro in a Streptococcus mutans Biofilm Model.

Genetic studies have shown that variations in enamel formation genes are associated with caries susceptibility. The aim of this study was to test in vitro whether variants in these genes are associated with dental enamel demineralization in a Streptococcus mutans biofilm model. DNA and enamel samples were obtained from 213 individuals. DNA was extracted from saliva, and 16 single nucleotide polymorphisms were analyzed. The physical and chemical properties of sound enamel samples and the mineral loss and the lesion depth of the demineralized enamel samples under cariogenic challenge were analyzed. Microhardness, enamel chemicals, mineral loss and demineralization depth were compared between different genotypes at each single nucleotide polymorphism. The GG genotype of TUFT1 (rs17640579) and the GT genotype of MMP20 (rs1612069) exhibited increased microhardness (p = 0.044 and 0.016, respectively). The GG genotype of AMBN (rs7694409) had a higher magnesium level, while the CT genotype of TFIP11 (rs2097470) had a lower magnesium level (p = 0.044 and 0.046, respectively). The GT genotype of MMP20 (rs1612069) had a higher calcium level (p = 0.034). The GG genotype of AMBN (rs13115627), the AG genotype of ENAM (rs12640848) and the AA genotype of MMP20 (rs2292730) had a lower phosphorus level (p = 0.012, 0.006, and 0.023, respectively). The GG genotype of AMBN (rs13115627) was also associated with a higher calcium-phosphorus ratio (p = 0.034). Individuals with the CC genotype of TFIP11 (rs134143) exhibited significantly more mineral loss (p = 0.011) and a deeper lesions (p = 0.042). Individuals with the TT genotype of TFIP11 (rs2097470) had more mineral loss (p = 0.018). Individuals with the GG genotype of TUFT1 (rs17640579) exhibited a shallower demineralization depth (p = 0.047). Individuals with the GT genotype of MMP20 (rs1612069) exhibited a shallower demineralization depth (p = 0.042). Individuals with the GG genotype of ENAM (rs12640848) exhibited less mineral loss (p = 0.01) and a shallower demineralization depth (p = 0.03). Genetic variations in TFIP11, TUFT1, MMP20, and ENAM influenced enamel demineralization in a Streptococcus mutans biofilm model.

Gambogic acid-loaded biomimetic nanoparticles in colorectal cancer treatment.

Gambogic acid (GA) is expected to be a potential new antitumor drug, but its poor aqueous solubility and inevitable side effects limit its clinical application. Despite these inhe rent defects, various nanocarriers can be used to promote the solubility and tumor targeting of GA, improving antitumor efficiency. In addition, a cell membrane-coated nanoparticle platform that was reported recently, unites the customizability and flexibility of a synthetic copolymer, as well as the functionality and complexity of natural membrane, and is a new synthetic biomimetic nanocarrier with improved stability and biocompatibility. Here, we combined poly(lactic-co-glycolic acid) (PLGA) with red blood-cell membrane (RBCm), and evaluated whether GA-loaded RBCm nanoparticles can retain and improve the antitumor efficacy of GA with relatively lower toxicity in colorectal cancer treatment compared with free GA. We also confirmed the stability, biocompatibility, passive targeting, and few side effects of RBCm-GA/PLGA nanoparticles. We expect to provide a new drug carrier in the treatment of colorectal cancer, which has strong clinical application prospects. In addition, the potential antitumor drug GA and other similar drugs could achieve broader clinical applications via this biomimetic nanocarrier.

Enhancement of radiotherapy efficacy by pleiotropic liposomes encapsulated paclitaxel and perfluorotributylamine.

Paclitaxel (PTX) is widely used as a radiosensitizer in the clinical treatment of cancer. However, the efficacy of chemoradiotherapy is limited by the hostility of the tumor microenvironment such as hypoxia. To overcome this constraint, we designed pleiotropic radiotherapy sensitized liposomes containing perfluorotributylamine (PFTBA) and PTX. The results showed that liposomes significantly accumulated in the tumor site. PFTBA in liposomes dramatically reversed tumor hypoxia and improved the sensitivity of tumor radiotherapy. PTX in liposomes blocked the cell cycle of tumor cells in the radiation-sensitive G2/M phase, which was even greater when combined with PFTBA. In vitro and in vivo tumor treatment further demonstrated remarkably improved therapeutic outcomes in radiotherapy with such biocompatible liposomes. In conclusion, the pleiotropic liposomes encapsulated PFTBA and PTX provide significant radiotherapy sensitization and show promise for future application in clinical medicine.

Symptoms and signs of temporomandibular disorders in patients with knee osteoarthritis.

OBJECTIVES: Both temporomandibular disorder (TMD) and knee osteoarthritis (KOA) are prevalent joint diseases; however, an association between them has not been reported. Therefore, this study investigated the prevalence of the specific symptoms and signs of TMDs (SSTs) in patients with KOA. METHODS: In total, 200 patients with KOA and 150 healthy individuals were recruited. The prevalence of specific SSTs in patients with mild or severe KOA was compared with the prevalence of specific SSTs in the control group and the results were analysed using a chi-square test. Logistic regression was used to adjust for potential confounders, such as gender and age. RESULTS: The prevalence of 'impaired range of jaw movement (IRM)' was 63.6% (n = 77) in the mild KOA group and 62.4% (n = 117) in the severe KOA group; the values for both KOA groups were significantly higher than that for the non-OA control group (34.7%, n = 144; P < 0.017). In addition, 54.7% of the patients with severe KOA reported 'impaired temporomandibular joint (TMJ) function', a value significantly higher than that of the control group (39.6%, P < 0.017). No significant differences between groups were found for other SSTs. CONCLUSIONS: Patients with KOA might be more likely to experience SSTs, such as IRM and impaired TMJ function.

Enhancement of radiotherapy efficacy by docetaxel-loaded gelatinase-stimuli PEG-Pep-PCL nanoparticles in gastric cancer.

Docetaxel (DOC) is widely used as radiosensitizer in various tumors, including gastric cancer (GC), but its therapeutic effect remains to be improved. In this study, using docetaxel-loaded nanoparticles (DOC-NPs) based on gelatinase-stimuli strategy, we compared their radioenhancement efficacy with docetaxel in GC. Compared with DOC, radiosensitization of DOC-NPs was improved significantly (sensitization enhancement ratio increased 1.09-fold to 1.24-fold, P<0.01) in all three gelatinase overexpressing GC cells, while increased slightly (1.02-fold, P=0.38) in gelatinase deficient normal gastric mucosa cells. The improved radiosensitization efficacy was associated with enhanced G2/M arrest, increased reactive oxygen species (ROS), more effective DSBs and promoted apoptosis. More importantly, the radiosensitization efficacy of DOC-NPs (estimated as ''very active'') was more prominent than DOC (estimated as ''moderately active'') by intravenous injection in xenograft. In conclusion, DOC-NPs are highly selective radiosensitizers in gelatinase over-expressing tumors, and more effective than DOC. By manipulating the common microenvironment difference between tumor and normal tissue, gelatinase-mediated nanoscale delivery system serves as a potential strategy possessing both universality and selectivity for radiosensitizers.