A Novel Bioswitchable miRNA Mimic Delivery System: Therapeutic Strategies Upgraded from Tetrahedral Framework Nucleic Acid System for Fibrotic Disease Treatment and Pyroptosis Pathway Inhibition.

There has been considerable interest in gene vectors and their role in regulating cellular activities and treating diseases since the advent of nucleic acid drugs. MicroRNA (miR) therapeutic strategies are research hotspots as they regulate gene expression post-transcriptionally and treat a range of diseases. An original tetrahedral framework nucleic acid (tFNA) analog, a bioswitchable miR inhibitor delivery system (BiRDS) carrying miR inhibitors, is previously established; however, it remains unknown whether BiRDS can be equipped with miR mimics. Taking advantage of the transport capacity of tetrahedral framework nucleic acid (tFNA) and upgrading it further, the treatment outcomes of a traditional tFNA and BiRDS at different concentrations on TGF-ß- and bleomycin-induced fibrosis simultaneously in vitro and in vivo are compared. An upgraded traditional tFNA is designed by successfully synthesizing a novel BiRDS, carrying a miR mimic, miR-27a, for treating skin fibrosis and inhibiting the pyroptosis pathway, which exhibits stability and biocompatibility. BiRDS has three times higher efficiency in delivering miRNAs than the conventional tFNA with sticky ends. Moreover, BiRDS is more potent against fibrosis and pyroptosis-related diseases than tFNAs. These findings indicate that the BiRDS can be applied as a drug delivery system for disease treatment.

A nomogram prediction of implant apical non-coverage on bone-added transcrestal sinus floor elevation: A retrospective cohort study.

OBJECTIVES: To identify the risk indicators and develop and validate a nomogram prediction model of implant apical non-coverage by comprehensively analyzing clinical and radiographic factors in bone-added transcrestal sinus floor elevation (TSFE). MATERIAL AND METHODS: A total of 260 implants in 195 patients receiving bone-added TSFE were included in the study. The population was divided into a development (180 implants) and a validation (80 implants) cohort. According to 6 months post-surgery radiographic images, implants were categorized as "apical non-coverage" or "apical covered." The association of risk factors including clinical and radiographic parameters with implant apical non-coverage was assessed using regression analyses. A nomogram prediction model was developed, and its validation and discriminatory ability were analyzed. RESULTS: The nomogram predicting bone-added TSFE's simultaneously placed implant's apex non-coverage after 6 months. This study revealed that sinus angle, endo-sinus bone gain, implant protrusion length, graft contact walls, and distal angle were predictors of implant apical non-coverage. The generated nomogram showed a strong predictive capability (area under the curve [AUC] = 0.845), confirmed by internal validation using 10-fold cross-validation (Median AUC of 0.870) and temporal validation (AUC = 0.854). The calibration curve and decision curve analysis demonstrated good performance and high net benefit of the nomogram, respectively. CONCLUSIONS: The clinical implementation of the present nomogram is suitable for predicting the apex non-coverage of implants placed simultaneously with bone-added TSFE after 6 months.

Effectiveness and complications of transcrestal sinus floor elevation using the cushioned grind-out technique: A retrospective cohort study with up to 7 years of follow-up.

AIM: To evaluate the effectiveness and complications of the cushioned grind-out technique. The primary outcome was endo-sinus bone gain (ESBG), while secondary outcomes included the Schneiderian membrane perforation rate and mid- to long-term implant survival. MATERIALS AND METHODS: In this retrospective study, we compared the cushioned grind-out technique with the classic osteotome technique, establishing statistical models to assess ESBG, membrane perforation rate and implant survival rate. RESULTS: A total of 259 patients and 340 implants were included. The mean ESBG was 5.31 mm for the cushioned grind-out group and 4.64 mm for the osteotome group. Multivariable regression analysis revealed that the cushioned grind-out technique significantly facilitated ESBG (p = .028). Nineteen preparation sites experienced membrane perforation, with rates of 5.5% and 6.4% for the cushioned grind-out and osteotome groups, respectively. However, the difference was not statistically significant (p = .920). Additionally, the cumulative survival rate of the implants for 7 years was 95.2% and 91.4%, respectively, with the surgical technique not significantly influencing the results. CONCLUSIONS: With 6 months to 7 years of post-prosthetic restoration review data, our findings show that the cushioned grind-out technique facilitates a higher ESBG, with no significant difference in membrane perforation or implant failure rate.

Cushioned grind-out technique transcrestal sinus floor elevation for simultaneous implantation in severe atrophic maxilla: A retrospective study with up to 7 years of follow-up.

OBJECTIVES: This study aimed to evaluate the effects of the cushioned grind-out technique transcrestal sinus floor elevation for simultaneous implant placement with ≤4 mm of residual bone height (RBH). MATERIALS AND METHODS: This was a retrospective propensity score matching (PSM) study. Five PSM analyses included the confounding variables of Schneiderian membrane perforation, early and late implant failure, and peri-implant apical and marginal bone resorption. After PSM, we compared the difference in five aspects between the RBH ≤ 4 and >4 mm groups. RESULTS: A total of 214 patients with 306 implants were included in this study. After PSM, the generalized linear mixed model (GLMM) indicated that RBH ≤ 4 mm had no significantly higher risk of Schneiderian membrane perforation and early and late implant failure (p = .897, p = .140, p = .991, respectively). The implant cumulative 7-year survival rate of the RBH ≤ 4 and >4 mm groups was 95.5% and 93.9%, respectively (log-rank test: p = .900). Within at least 40 cases per group after PSM, two multivariate GLMMs indicated that RBH ≤ 4 mm could not be identified as the promotive factor of bone resorption of either endo-sinus bone gain or crest bone level (RBH × time interaction p = .850, p = .698, respectively). CONCLUSIONS: Within the limitations, 3 months to 7 years of post-prosthetic restoration review data indicated an acceptable mid-term survival and success rate of applying the cushioned grind-out technique in RBH ≤ 4 mm cases.

Caffeic Acid Phenethyl Ester (CAPE) Inhibits Cross-Kingdom Biofilm Formation of Streptococcus mutans and Candida albicans.

Streptococcus mutans and Candida albicans exhibit strong cariogenicity through cross-kingdom biofilm formation during the pathogenesis of dental caries. Caffeic acid phenethyl ester (CAPE), a natural compound, has potential antimicrobial effects on each species individually, but there are no reports of its effect on this dual-species biofilm. This study aimed to explore the effects of CAPE on cariogenic biofilm formation by S. mutans and C. albicans and the related mechanisms. The effect of CAPE on planktonic cell growth was investigated, and crystal violet staining, the anthrone-sulfuric acid assay and confocal laser scanning microscopy were used to evaluate biofilm formation. The structures of the formed biofilms were observed using scanning electron microscopy. To explain the antimicrobial effect of CAPE, quantitative real-time PCR (qRT-PCR) was applied to monitor the relative expression levels of cariogenic genes. Finally, the biocompatibility of CAPE in human oral keratinocytes (HOKs) was evaluated using the CCK-8 assay. The results showed that CAPE suppressed the growth, biofilm formation and extracellular polysaccharides (EPS) synthesis of C. albicans and S. mutans in the coculture system of the two species. The expression of the gtf gene was also suppressed by CAPE. The efficacy of CAPE was concentration dependent, and the compound exhibited acceptable biocompatibility. Our research lays the foundation for further study of the application of the natural compound CAPE as a potential antimicrobial agent to control dental caries-associated cross-kingdom biofilms. IMPORTANCE Severe dental caries is a multimicrobial infectious disease that is strongly induced by the cross-kingdom biofilm formed by S. mutans and C. albicans. This study aimed to investigate the potential of caffeic acid phenethyl ester (CAPE) as a natural product in the prevention of severe caries. This study clarified the inhibitory effect of CAPE on cariogenic biofilm formation and the control of cariogenic genes. It deepens our understanding of the synergistic cariogenic effect of S. mutans and C. albicans and provides a new perspective for the prevention and control of dental caries with CAPE. These findings may contribute to the development of CAPE as a promising antimicrobial agent targeting this caries-related cross-kingdom biofilm.