The application of drug behavior management methods in the treatment of dental fear and oral diseases in children: A review.

Oral behavior management methods include basic behavior management methods and drug behavior management methods. In many cases, dental treatment that cannot be done simply through basic behavior management is not possible. The uncooperative behavior of children with dental fear in oral treatment has increased the demand for medication based behavior management methods. Drug sedation can provide more effective analgesic and anti-anxiety effects, thereby helping to provide comfortable, efficient, and high-quality dental services. This article will review the drug sedation methods selected in clinical treatment of pediatric dental fear in recent years, as well as the safety and effectiveness of commonly used drugs, in order to provide guidance for dental professionals in clinical practice.

DNA methyltransferase 3A induces the occurrence of oral submucous fibrosis by promoting the methylation of the von Hippel-Lindau.

BACKGROUND: Oral submucous fibrosis (OSF) is associated with malignant disorders. DNA methyltransferase 3A (DNMT3A) is a DNA methylesterase reported to be upregulated in multiple organs and shown to inhibit fibrosis. However, the detailed effect of DNMT3A on OSF remains unclear. METHODS: To mimic OSF in vitro, oral fibroblasts were exposed to arecoline and molecular biological experiments were performed to detect the function of DNMT3A in OSF. RESULTS: We found that von Hippel-Lindau (VHL) was downregulated and highly methylated in OSF. Arecoline remarkably increased the viability, invasiveness, and migration of oral fibroblasts, but upregulation of VHL partially reversed these effects. DNMT3A induces DNA hypermethylation in the VHL promoter, and VHL markedly inhibits the level of tenascin-C (TNC) by inducing the ubiquitination of TNC. TNC reversed the inhibitory effect of VHL upregulation on the differentiation of oral fibroblasts into myofibroblasts. CONCLUSION: DNMT3A induces OSF by promoting methylation of the VHL promoter. Hence, our study provides novel insights into the discovery of novel strategies that can be employed against OSF.

Knockdown of Notch Suppresses Epithelial-mesenchymal Transition and Induces Angiogenesis in Oral Submucous Fibrosis by Regulating TGF-ß1.

Oral submucous fibrosis (OSF) is a chronic disorder with a high malignant transformation rate. Epithelial-mesenchymal transition (EMT) and angiogenesis are key events in OSF. The Notch signaling plays an essential role in the pathogenesis of various fibrotic diseases, including OSF. Our study aimed to explore the effects of Notch on the EMT and angiogenesis processes during the development of OSF. The expression of Notch in OSF tissues versus normal buccal mucosa samples was compared. Arecoline was used to induce myofibroblast transdifferentiation of buccal mucosal fibroblasts (BMFs). Short hairpin RNA technique was used to knockdown Notch in BMFs. Pirfenidone and SRI-011381 were used to inhibit and activate the TGF-ß1 signaling pathway in BMFs, respectively. The expression of Notch was markedly upregulated in OSF tissues and fibrotic BMFs. Knockdown of Notch significantly decreased the viability and promoted apoptosis in BMFs subjected to arecoline stimulation. Downregulation of Notch also significantly suppressed the EMT process, as shown by the reduction of N-cadherin and vimentin with concomitant upregulation of E-cadherin. In addition, knockdown of Notch upregulated VEGF and enhanced the angiogenic activity of fBMFs. Moreover, inhibition of TGF-ß1 suppressed viability and EMT, promoted apoptosis, and induced angiogenesis of fBMFs, while activation of TGF-ß1 significantly diminished the effects of Notch knockdown on fBMFs. Knockdown of Notch suppressed EMT and induced angiogenesis in OSF by regulating TGF-ß1, suggesting that the Notch-TGF-ß1 pathway may serve as a therapeutic intervention target for OSF.

Stem cell-based therapy in periodontal regeneration: a systematic review and meta-analysis of clinical studies.

BACKGROUND: Periodontitis is a common and chronic inflammatory disease characterized by irreversible destruction of the tooth surrounding tissues, especially intrabony defects, which eventually lead to tooth loss. In recent years, stem cell-based therapy for periodontitis has been gradually applied to the clinic, but whether stem cell-based therapy plays a positive role in periodontal regeneration is unclear at present. METHODS: The clinical studies related to the evaluation of mesenchymal stem cells for periodontal regeneration in PubMed, Cochrane Central Register of Controlled trials (CENTRAL), Web of Science (WOS), Embase, Scopus, Wanfang and China national knowledge infrastructure (CNKI) databases were searched in June 2023. The inclusion criteria required the studies to compare the efficacy of stem cell-based therapy with stem cell free therapy for the treatment periodontitis, and to have a follow-up for at least six months. Two evaluators searched, screened, and assessed the quality and the risk of bias in the included studies independently. Review Manager 5.4 software was used to perform the meta-analysis, and GRADEpro GDT was used to evaluate the level of the evidence. RESULTS: Five randomized controlled trials (RCTs) including 118 patients were analyzed. The results of this meta-analysis demonstrated that stem cell-based therapy showed better therapeutic effects on clinical attachment level (CAL) (MD = - 1.18, 95% CI = - 1.55, - 0.80, P < 0.00001), pocket probing depth (PPD) (MD = - 0.75, 95% CI = - 1.35, - 0.14, P = 0.020), and linear distance from bone crest to bottom of defect (BC-BD)( MD = - 0.95, 95% CI = - 1.67, - 0.23, P = 0.010) compared with cell-free group. However, stem cell-based therapy presented insignificant effects on gingival recession (P = 0.14), linear distance from cementoenamel junction to bottom of defect (P = 0.05). CONCLUSION: The results demonstrate that stem cell-based therapy may be beneficial for CAL, PPD and BC-BD. Due to the limited number of studies included, the strength of the results in this analysis was affected to a certain extent. The high-quality RCTs with large sample size, multi-blind, multi-centric are still required, and the methodological and normative clinical study protocol should be established and executed in the future.

Star-shaped incision technique for gingiva patients treated with implant-supported fixed prosthesis.

To evaluate the modified star-shaped incision on gingival sulcus for reducing horizontal food impaction around implant-supported restoration. Total 24 patients receiving bone-level implant placement were enrolled, a star-shaped incision was made on the gingiva sulcus before the placement of zirconia crown. Follow-up examination was carried out 3 and 6 months after final restoration, respectively. Assessment of soft tissue includes papilla height, modified plaque index, modified sulcus bleeding index, periodontal depth, gingival biotype and gingival margin level. Marginal bone level was measured on periapical radiographs. Only 1 patient complained about the horizontal food impaction. Both the mesial and distal papilla almost filled the entire proximal space, in good harmony with the adjacent papillae. No recession of the gingival margin was found around the crown even in the patients with thin gingival biotype. Other parameters of soft tissue including modified plaque index, modified sulcus bleeding index and periodontal depth remained low during the whole follow-up visit. The resorption of marginal crestal bone was less than 0.6 mm during the first 6 month, and there was no significant difference among baseline, 3-month and 6-month visit. The modified star-shaped incision on the gingiva sulcus maintained the gingival papilla height and reduced the occurrence of horizontal food impaction, and no recession of the gingiva margin was found around implant-supported restoration.

Nobiletin sensitizes colorectal cancer cells to oxaliplatin by PI3K/Akt/MTOR pathway.

Oxaliplatin is one of the most common chemotherapy drugs for colorectal cancer (CRC), but its application is greatly limited owing to the drug resistance. Nobiletin is a natural flavonoid isolated from citrus peel and has many biological functions, including anti-inflammatory, antitumor and neuroprotective activities. However, little is known about the effect of nobiletin on the anti-tumor activities of other chemotherapy drugs. In this study, we examined the effect of nobiletin on the efficacy of oxaliplatin in treatment of CRC by using two CRC cell lines. In vitro experiments indicated that nobiletin enhanced the inhibitory effect of oxaliplatin on the proliferation of CRC cells. Meanwhile, nobiletin promoted oxaliplatin-induced apoptosis of CRC cells, as demonstrated by the increased expression of pro-apoptotic proteins (Bax and cleaved-caspse3) and the down-regulation of anti-apoptotic protein Bcl-2. Mechanically, nobiletin sensitized CRC to oxaliplatin chemotherapy by down-regulating the PI3K/Akt/mTOR pathway. Taken together, our study has demonstrated that nobiletin could enhance the sensitivity of CRC to oxaliplatin chemotherapy, and provided a molecular basis for nobiletin's potential applications in the chemosensitization of CRC.