Nanocatalysts for modulating antitumor immunity: fabrication, mechanisms and applications.

Immunotherapy harnesses the inherent immune system in the body to generate systemic antitumor immunity, offering a promising modality for defending against cancer. However, tumor immunosuppression and evasion seriously restrict the immune response rates in clinical settings. Catalytic nanomedicines can transform tumoral substances/metabolites into therapeutic products in situ, offering unique advantages in antitumor immunotherapy. Through catalytic reactions, both tumor eradication and immune regulation can be simultaneously achieved, favoring the development of systemic antitumor immunity. In recent years, with advancements in catalytic chemistry and nanotechnology, catalytic nanomedicines based on nanozymes, photocatalysts, sonocatalysts, Fenton catalysts, electrocatalysts, piezocatalysts, thermocatalysts and radiocatalysts have been rapidly developed with vast applications in cancer immunotherapy. This review provides an introduction to the fabrication of catalytic nanomedicines with an emphasis on their structures and engineering strategies. Furthermore, the catalytic substrates and state-of-the-art applications of nanocatalysts in cancer immunotherapy have also been outlined and discussed. The relationships between nanostructures and immune regulating performance of catalytic nanomedicines are highlighted to provide a deep understanding of their working mechanisms in the tumor microenvironment. Finally, the challenges and development trends are revealed, aiming to provide new insights for the future development of nanocatalysts in catalytic immunotherapy.

Amelogenesis imperfecta in a Chinese family resulting from a FAM83H variation and the effect of FAM83H on the secretion of enamel matrix proteins.

OBJECTIVES: To investigate the variant of an amelogenesis imperfecta (AI) family and to explore the function of the FAM83H (family with sequence similarity 83 member H) in the enamel formation. MATERIALS AND METHODS: We investigated a five-generation Chinese family diagnosed with AI; clinical data was collected, whole-exome sequencing (WES) was conducted to explore the pathogenic gene and variants and Sanger sequencing was used to verify the variants. The three-dimensional protein structures of wild-type and mutant FAM83H were predicted using alpha fold 2. To study the possible regulatory function of Fam83h on amelogenesis, immunolocalization was performed to observe the expression of Fam83h protein in Sprague-Dawley rat postnatal incisors. The mRNA and protein level of amelogenin, enamelin, kallikrein-related peptidase-4 and ameloblastin were also detected after the Fam83h was knocked down by small interfering RNA (siRNA) in HAT-7 cells. RESULTS: A known nonsense variant (c.973 C > T) in exon 5 of FAM83H gene was found in this family, causing a truncated protein (p.R325X). Immunolocalization of Fam83h in Sprague-Dawley rat postnatal incisors showed that Fam83h protein expression was detected in presecretory and secretory stages. When Fam83h expression was reduced by siRNA, the expression of amelogenin, enamelin, kallikrein-related peptidase-4 decreased. However, the expression of ameloblastin increased. CONCLUSIONS: FAM83H gene variant (c.973 C > T) causes AI. FAM83H regulates the secretion of enamel matrix proteins and affects ameloblast differentiation. CLINICAL RELEVANCE: This study provided that FAM83H variants could influence enamel formation and provided new insights into the pathogenesis of AI.

Effects of bonded spurs, fixed and removable palatal crib in the early treatment of anterior open bite: A systematic review and meta-analysis.

INTRODUCTION: Bonded spurs, fixed or removable palatal cribs have been used to treat anterior open bite (AOB) in growing children. Different conclusions have been brought out by different authors. This meta-analysis aimed to evaluate the effect of bonded spurs, fixed and removable palatal cribs in the early treatment of AOB. METHODS: A comprehensive electronic search was carried out through PubMed, Embase (via Ovid), MEDLINE (via Ovid), Cochrane Central Register of Controlled Trials, and Web of Science up to May 1, 2022. This meta-analysis was performed in accordance with the Cochrane Handbook for Systematic Reviews of Interventions. The work was carried out by 2 reviewers in duplicate and independently, including electronic searching, data extracting, risk of bias assessment, quality of evidence grading, heterogeneity and statistical power analysis, and eligibility evaluation of the retrieved articles. RESULTS: Four studies out of 181 articles were recruited in the meta-analysis after applying the inclusion and exclusion criteria. The results showed that bonded lingual spurs and fixed palatal crib or spurs produced similar overbite changes (mean difference, -0.32; 95% confidence interval, -1.06 to 0.43; P = 0.41; I2 = 27%; meta power = 0.099). Fixed palatal crib and removable palatal crib also exhibited comparable effects in correcting AOB (mean difference, -0.02; 95% confidence interval, -0.90 to 0.86; P = 0.96; I2 = 0%; meta power = 0.2182). The quality of evidence about these 2 outcomes assessed with GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) was low. CONCLUSIONS: Bonded lingual spurs, fixed palatal crib or spurs, and removable palatal crib had similar effects in the early treatment of AOB. Because the number of included studies was limited and only the overbite changes before and after treatment were assessed, more clinical randomized controlled studies with longer follow-ups are needed to get more clinically significant advice.

Survival analysis of pulpectomy in primary molars performed under dental general anaesthesia: a two-year retrospective study.

BACKGROUND: To retrospectively investigate the success rate of primary-molar pulpectomy performed under general anaesthesia and the potential risk factors that affect the 24-month success rate. METHODS: The case data and two-year follow-up records of children (aged 3-6 years) who received pulpectomy in primary molars performed under general anaesthesia were reviewed and assessed. Potential risk factors included age, gender, decayed-missing-filled teeth, endodontic diagnosis, tooth location, and postobturation sealing of the pulp chamber floor with MTA. With a two-year follow-up period, the outcomes of all the primary molars were classified into success and failure. Survival analysis was used to assess the outcomes. The Kaplan-Meier method was used to analyse the success rate. Univariate and multivariate Cox proportional hazards regression models were used to evaluate the potential risk factors associated with the overall survival of primary molars. RESULTS: A total of 410 teeth from 163 children (88 boys and 75 girls) were included in this study. The overall two-year success rate was 66.1% for all primary molars. The mean overall survival time for this study was 22.1 (95% CI, 21.73‒22.48) months. Multivariate Cox regression analysis demonstrated that endodontic diagnosis (irreversible pulpitis or periapical periodontitis), tooth location (maxillary or mandibular primary molar), and postobturation sealing of the pulp chamber floor (MTA or no-MTA) were significant risk factors for overall survival in this study (P < .05). The differences in success rates were not statistically significant in terms of age, gender, and decayed-missing-filled teeth (P > .05). CONCLUSIONS: When compared to teeth diagnosed with irreversible pulpitis, those with periapical periodontitis failed more frequently. Postobturation sealing of the pulp chamber floor with MTA improved the success rate of pulpectomy in primary molars, especially when the inflammation did not spread to the periradicular area.

FoxO1 Agonists Promote Bone Regeneration in Periodontitis by Protecting the Osteogenesis of Periodontal Ligament Stem Cells.

Protecting the function of periodontal ligament stem cells (PDLSCs) is crucial for bone regeneration in periodontitis. Forkhead box protein O1 (FoxO1) has been previously reported as a crucial mediator in bone homeostasis, providing a favorable environment for osteoblast proliferation and differentiation. In this study, we investigated the effect and mechanism of FoxO1 agonists on the osteogenesis of PDLSCs under inflammatory conditions. In this study, we screened FoxO1 agonists by detecting their effects on the osteogenic differentiation of PDLSCs. Then, the function of these agonists in bone regeneration was analyzed in the periodontitis model. We found that hyperoside or 2-furoyl-LIGRLO-amide trifluoroacetate salt (2-Fly) promoted osteogenic differentiation under inflammation by simultaneously inhibiting nuclear factor κB (NF-κB) activation, ß-catenin expression, and reactive oxygen species (ROS) production. Moreover, local injection of hyperoside or 2-Fly rescued the expression of FoxO1 and runt-related transcription factor 2 (Runx2) in vivo, alleviating alveolar bone loss and periodontal ligament damage. These findings suggested that FoxO1 agonists exerted a protective effect on osteogenesis in PDLSCs, as a result, facilitating bone formation under inflammatory conditions. Taken together, FoxO1 might serve as a therapeutic target for bone regeneration in periodontitis by mediating multiple signaling pathways.